Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genom...Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genome.Mitochondrial transcription termination factors(mTERFs)are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts.Despite their recognized importance,the specific roles of mTERF proteins in maize remain largely unexplored.Here,we clone and functionally characterize the maize mTERF18 gene.Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos,resulting in abortive phenotypes.Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18.We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests.mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein.Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene,leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity.Furthermore,transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects.Collectively,these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.展开更多
Chlorogenic acid(CGA),a potent antioxidant with antimicrobial,antiviral,and metabolic regulatory properties,plays multifunctional roles in apple fruit by enhancing postharvest quality,extending shelf life through oxid...Chlorogenic acid(CGA),a potent antioxidant with antimicrobial,antiviral,and metabolic regulatory properties,plays multifunctional roles in apple fruit by enhancing postharvest quality,extending shelf life through oxidative stress reduction,and inhibiting enzymatic browning to preserve color,flavor,and nutritional integrity.Despite the established role of hydroxycinnamoyl transferase(HCT)as a rate-limiting enzyme in CGA biosynthesis,the specific HCT gene responsible for this process and its regulatory mechanisms remain elusive.To address this knowledge gap,we systematically investigated CGA accumulation dynamics during apple storage and functionally characterized MdHCT6,a candidate gene within the HCT family.We found that the chlorogenic acid content in apple fruit increased significantly during postharvest storage compared with the initial storage.Transcriptome analysis showed that the expression level of MdHCT6 was significantly higher than that of other HCT homologues,which was consistent with the reverse transcription quantitative PCR(RT-qPCR)results.In vitro enzymatic assays demonstrated that MdHCT6 catalyzes the synthesis of chlorogenic acid using shikimic acid and quinic acid as precursors,while genetic evidence confirmed its role as a key positive regulator of chlorogenic acid accumulation in apples.Furthermore,we identified the transcription factor MdMYB93 as a direct upstream activator of MdHCT6,establishing a regulatory cascade that governs CGA production.This work not only deciphers the molecular hierarchy of CGA biosynthesis in apples but also provides actionable targets for genetic improvement of antioxidant capacity and postharvest resilience in apple germplasm.展开更多
Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches ofte...Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.展开更多
BACKGROUND Esophageal cancer(ESCA)poses a significant challenge in oncology because of the limited treatment options and poor prognosis.Therefore,enhancing the therapeutic effects of radiotherapy for ESCA and identify...BACKGROUND Esophageal cancer(ESCA)poses a significant challenge in oncology because of the limited treatment options and poor prognosis.Therefore,enhancing the therapeutic effects of radiotherapy for ESCA and identifying relevant therapeutic targets are crucial for improving both the survival rate and quality of life of patients.AIM To define the role of the transcription factor Snail family transcriptional repressor 1(SNAI1)in ESCA,particularly its regulation of radiosensitivity.METHODS A comprehensive analysis of TCGA data assessed SNAI1 expression in ESCA.Survival curves correlated SNAI1 levels with radiotherapy outcomes.Colony formation assays,flow cytometry,and a xenograft model were used to evaluate tumor radiosensitivity and apoptosis.Western blot validated protein expression,while Chromatin im-munoprecipitation assays examined SNAI1's role in regulating epithelial-mesenchymal transition(EMT).RESULTS SNAI1 expression in ESCA cell lines and clinical specimens emphasizes its central role in this disease.Elevated SNAI1 expression is correlated with unfavorable outcomes in radiotherapy.Downregulation of SNAI1 enhances the sensitivity of ESCA cells to ionizing radiation(IR),resulting in remarkable tumor regression upon IR treatment in vivo.This study underscores the direct involvement of SNAI1 in the regulation of EMT,particularly under IR-induced conditions.Furthermore,inhibiting deacetylation effectively suppresses EMT,suggesting a potential avenue to enhance the response to radiotherapy in ESCA.CONCLUSION This study highlights SNAI1's role in ESCA radiosensitivity,offering prognostic insights and therapeutic strategies to enhance radiotherapy by targeting SNAI1 and modulating EMT processes.展开更多
Northern blot analysis was conducted with mitochondrial RNA from seedling leaves, floral buds, and developing seeds of NCa CMS, maintainer line and fertile F1 using ten mitochondrial genes as probes. The results revea...Northern blot analysis was conducted with mitochondrial RNA from seedling leaves, floral buds, and developing seeds of NCa CMS, maintainer line and fertile F1 using ten mitochondrial genes as probes. The results revealed that 9 out of the 10 mitochondrial genes, except for atp6, showed no difference in different tissues of the corresponding materials of NCα CMS system and that they might be constitutively expressed genes. Eight genes, such as orf139, orf222, atpl, cox1, cox2, cob, rm5S, and rm26S, showed no difference among the three tissues of all the materials detected. So the expression of these eight genes was not regulated by nuclear genes and was not tissue-specific. The transcripts of atp9 were identical among different tissues, but diverse among different materials, indicating that transcription of atp9 was neither controlled by nuclear gene nor tissue-specific. Gene atp6 displayed similar transcripts with the same size among different tissues of all the materials but differed in abundance among tissues of corresponding materials and its expression might be tissue-specific under regulation of nuclear gene. Moreover, three transcripts of orf222 were detected in the floral buds of NCa cms and fertile F1, but no transcript was detected in floral buds of the maintainer line.The transcription of orf139 was similar to that of orf222 but only two transcripts of 0.8 kb and 0.6 kb were produced. The atp9 probe detected a single transcript of 0.6 kb in NCa cms and in maintainer line and an additional transcript of 1.2 kb in fertile F1. The relationship of expression of orf222, orf139, and atp9 with NCa sterility was discussed.展开更多
The peaT1 gene fragment was amplified from pGEM-6p-l-peaT1 by PCR, and recovered target gene was cloned into pLexA vector. After digestion and sequencing, the bait vector pLexA-peaT1 was transformed into yeast strain ...The peaT1 gene fragment was amplified from pGEM-6p-l-peaT1 by PCR, and recovered target gene was cloned into pLexA vector. After digestion and sequencing, the bait vector pLexA-peaT1 was transformed into yeast strain EGY48 [p8op-lacZ] by PEG/LiAC, and the transcriptional activity of bait vector was detected. The results showed that recombinant bait plasmid pLexA-PEMG1 was constructed, for the two bands of recombinant bait plasmid in agarose gel eleetrophoresis were expected after digesting by restriction endonuclease EcoR I and Xho I. Therefore, the recombinant bait plasmid could be used in yeast two-hybrid system to screen a cDNA library.展开更多
Auxins were the first of the major plant hormones and played key roles in plant growth and development.Auxin triggered gene expression through several mechanisms.The canonical textbook model is that auxin binds to TIR...Auxins were the first of the major plant hormones and played key roles in plant growth and development.Auxin triggered gene expression through several mechanisms.The canonical textbook model is that auxin binds to TIR1/AFB receptors and stabilizes their interaction with Aux/IAA repressors,leading to their ubiquitination and degradation,which results in activation of ARFs transcription factors.The recent study published in Nature by JiíFriml and co-authors updated the view on gene expression regulated by auxin.The role of TIR-produced cAMP was confirmed to be the second messenger in transcriptional auxin signaling.The conclusions raised in this Nature article shift the paradigm about the regulation of plant growth and development by auxin to the modulation of cAMP production and its interaction with candidate targets.展开更多
In climacteric fruits,the role of ethylene in promoting ripening process and its molecular regulatory mechanisms have been well elucidated.However,research into ethylene's roles in non-climacteric fruits has only ...In climacteric fruits,the role of ethylene in promoting ripening process and its molecular regulatory mechanisms have been well elucidated.However,research into ethylene's roles in non-climacteric fruits has only advanced in recent years,largely because these fruits produce much less ethylene than climacteric fruits.Consequently,reports on its molecular regulatory involvement are still limited.Grape(Vitis vinifera L.),one of the most economically valuable fruits,is regarded as a classical non-climacteric fruit.In this study,an enzyme participating in the last step of ethylene biosynthesis,VvACO1,has been identified as a key enzyme controlling ethylene release in grape fruits(Vitis vinifera‘Jingyan’and‘Red Balado’)using correlation analysis and enzymatic experiments.The transcriptional regulation of VvACO1 was investigated by integrating multiple methods such as DNA pull-down assays,co-expression analysis,dual luciferase reporting system,yeast one-hybrid assays,and transgenic experiments.Our findings revealed that the upregulation of VvACO1 in grape fruits was primarily caused by the removal of transcriptional inhibition.Remarkably,seven transcription factors(TFs)were identified as inhibitors of VvACO1,including VvHY5 from bZIP family,VvWIP2 from C2H2 family,VvBLH1 from Homeobox family,VvAG1 and VvCMB1 from MADS-box family,VvASIL1 and VvASIL2 from Trihelix family.These seven TFs were located in nuclei and exhibited transcriptional inhibition activity.Notably,VvAG1 and VvASIL2 could inhibit VvACO1 expression when overexpressed in grape leaves.Our findings provided theoretical clues for differences of ethylene release regulation between climacteric and non-climacteric fruits,also the identified seven TFs could be potential targets for grape molecular breeding.展开更多
Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has bee...Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.展开更多
Defensin,an essential component of plant development,is indispensable in pathogen resistance.However,the molecular function of defensins under pathological conditions of Cytospora canker has not been characterized in ...Defensin,an essential component of plant development,is indispensable in pathogen resistance.However,the molecular function of defensins under pathological conditions of Cytospora canker has not been characterized in apple plants.The present study exhibits a detailed overview of the phylogeny and structure of 29 defensins(MdDEF)in apple.Expression analysis revealed that MdDEF genes were spatiotemporally diverse across apple tissues.Five MdDEF genes were found to be significantly up-regulated following a challenge with Cytospora mali.The transgenic overexpression of five defensin genes in apple calli enhanced resistance to C.mali.Among them,MdDEF30 was strongly induced and conferred the highest resistance level in vivo.Meanwhile,antifungal activity assays in vitro demonstrated that a recombinant protein produced from MdDEF30could inhibit the growth of C.mali.Notably,MdDEF30 promoted the accumulation of reactive oxygen species(ROS)and activated defense-related genes such as PR4,PR10,CML13,and MPK3.Co-expression regulatory network analysis showed that MdWRKY75 may regulate the expression of MdDEF30.Further yeast onehybrid(Y1H),luciferase,and chromatin Immunoprecipitation quantitative polymerase chain reaction(ChIPqPCR)assays verified that MdWRKY75 could directly bind to the promoter of MdDEF30.Importantly,pathogen inoculation assays confirmed that MdWRKY75 positively regulates resistance by transcriptionally activating MdDEF30.Overall,these results demonstrated that MdDEF30 promotes resistance to C.mali in apple plants and that MdWRKY75 regulates MdDEF30 expression during the induction of resistance,thereby clarifying biochemical mechanisms of resistance to C.mali in apple trees.展开更多
Since transgene silencing was found in transgenic plants,many scholars have studied it extensively and considered that it has three functional mechanisms:post dependent gene silencing,transcriptional gene silencing,p...Since transgene silencing was found in transgenic plants,many scholars have studied it extensively and considered that it has three functional mechanisms:post dependent gene silencing,transcriptional gene silencing,post transcriptional gene silencing.At the moment,people have mainly focused on the study of post transcriptional gene silencing and found its features:extensivity,conduction and peculiarity,also put forward some hypothesis for its mechanisms,for example,RNA threshold model,aberrant RNA model,inter or intra molecular base pairing model and so on.Furthermore,post transcriptional gene silencing is being applied in gene engineering of plants.Recently the people have found that post transcriptional gene silencing has bearing on capacity plants resisting virus.Many researchers have studied post transcriptional gene silencing,but there are some questions which need be solved in the future.This article summarizes progresses in features,mechanisms,applies of post transcriptional gene silencing about transgenic plants.展开更多
While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from th...While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference(RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by noncoding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing(TGS), as well as finetuning their expression through post-transcriptional gene silencing(PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.展开更多
As part of our efforts to identify novel contraceptive targets in the epididymis we performed transcriptional profiling on each of the 10 and 19 segments of the mouse and rat epididymidis, respectively, using Affymetr...As part of our efforts to identify novel contraceptive targets in the epididymis we performed transcriptional profiling on each of the 10 and 19 segments of the mouse and rat epididymidis, respectively, using Affymetrix whole genome microarrays. A total of 17 096 and 16 360 probe sets representing transcripts were identified as being expressed in the segmented mouse and rat epididymal transcriptomes, respectively. Comparison of the expressed murine transcripts against a mouse transcriptional profiling database derived from 22 other mouse tissues identified 77 transcripts that were expressed uniquely in the epididymis. The expression of these genes was further evaluated by reverse transcription polymerase chain reaction （RT-PCR） analysis of RNA from 21 mouse tissues. RT-PCR analysis confirmed epididymis-specific expression of Defensin Beta 13 and identified two additional genes with expression restricted only to the epididymis and testis. Comparison of the 16 360 expressed transcripts in the rat epididymis with data of 21 other tissues from a rat transcriptional profiling database identified 110 transcripts specific for the epididymis. Sixty-two of these transcripts were further investigated by qPCR analysis. Only Defensin 22 （E3 epididymal protein） was shown to be completely specific for the epididymis. In addition, 14 transcripts showed more than 100-fold selective expression in the epididymis. The products of these genes might play important roles in epididymal and/or sperm function and further investigation and validation as contraceptive targets are warranted. The results of the studies described in this report are available at the Mammalian Reproductive Genetics （MRG） Database （http：//mrg. genetics.washington.edu/）. （Asian J Androl 2007July; 9： 522-527）展开更多
Retrotransposons account for a large proportion of the genome and genomic variation, and play key roles in creating novel genes and diversifying the genome in many eukaryotic species. Although retrotransposons are abu...Retrotransposons account for a large proportion of the genome and genomic variation, and play key roles in creating novel genes and diversifying the genome in many eukaryotic species. Although retrotransposons are abundant in plants, their roles had been underestimated because of a lack of research. Here, we characterized a gibberellin Acid (GA)-insensitive dwarf mutant, 84133, in foxtail millet. Map-based cloning revealed a 5.5-kb Copia-like retrotransposon insertion in DWARF1 (D1), which encodes a DELLA protein. Transcriptional analysis showed that the Copia retrotransposon mediated the transcriptional reprogramming of D1 leading to a novel N-terminal-deleted truncated DELLA transcript that was putatively driven by Copia's LTR, namely D1-TT, and another chimeric transcript. The presence of D1-TT was confirmed by protein immunodetection analysis. Furthermore, D1-TT protein was resistant to GA3 treatment compared with the intact DELLA protein due to its inability to interact with the GA receptor, SiGID1. Overexpression of D1-TT in foxtail millet resulted in dwarf plants, confirming that it determines the dwarfism of 84133. Thus, our study documents a rare instance of long terminal repeat (LTR) retrotransposon-mediated transcriptional reprograming in the plant kingdom. These results shed light on the function of LTR retrotransposons in generating new gene functions and genetic diversity.展开更多
Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELON...Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELONGATED HYPOCOTYL 5(HY5),a master regulator in the light signaling pathway,is required for normal fruit ripening in tomato(Solanum lycopersicum).Loss of function of tomato HY5(SlHY5)impairs pigment accumulation and ethylene biosynthesis.Transcriptome profiling identified 2948 differentially expressed genes,which included 1424 downregulated and 1524 upregulated genes,in the Slhy5 mutants.In addition,genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation.Surprisingly,the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants,and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins.Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes.These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery.Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.展开更多
Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosc...Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.展开更多
Starch biosynthesis is important during endosperm development. Much has been known for the regulation of gene expression involved in starch synthesis, less information is available on the genome-wide expression profil...Starch biosynthesis is important during endosperm development. Much has been known for the regulation of gene expression involved in starch synthesis, less information is available on the genome-wide expression profiles as a consequence of impaired starch synthesis. In this study, we examined the transcriptional responses through microarray analysis in an ae wx double-mutant with loss-of-function starch branching enzyme IIb （SBEIIb） and granule-bound starch synthase I （GBSSI）. Through Gene Ontology enrichment analysis, we identified differentially expressed genes （DEGs） involved in chromatin organization and lipid transport. The DEGs also include alcohol dehydrogenase genes and pyruvate decarboxylase genes involved in sugar metabolism. In summary, the ae wx double mutations caused pleiotropic effects and transcriptional changes for a number of genes involved in metabolism, cellular response and organization. Therefore, a block in starch synthesis triggers transcriptional responses to favour the flux of excess carbohydrates into glycolysis, pentose phosphate pathway, and cell wall biosynthesis, but not toward the synthesis of alternative storage compounds.展开更多
Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially s...Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.展开更多
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factor...Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.展开更多
Cellulose, a major constituent of plant biomass, is synthesized by a cellulose synthase complex. It has been demonstrated that MYB genes transcriptionally regulate cellulose synthase in Arabidopsis. However, little is...Cellulose, a major constituent of plant biomass, is synthesized by a cellulose synthase complex. It has been demonstrated that MYB genes transcriptionally regulate cellulose synthase in Arabidopsis. However, little is known about this process in tomato. Here, two MYB （SIMYB1/2） and three cellulose synthase （CESA） （SICESA41516） genes were isolated. SIMYB1/2 and SICESA4/5/6 accumulation was found to correspond to cellulose accumulation in different tissues of tomato. Dual luciferase assays indicated that these two MYBs were transcriptional activators that interact with promoters of SICESA4/5/6. Moreover, SIMYB2 could also activate promoters of SIMYB1/2, suggesting the possible underlying auto-activation mech- anisms for MYB transcription factors. Transient over-expression of SlMYB1/2 in Nicotiana tabacum up-regulated tobacco endogenous NtCESA genes and increased cellulose accumulation. The function of SIMYB112 was further investigated using stable transformation and the results indicated that N. tabacum lines heterologous expressing SIMYB1/2 displayed a pleiotropic phenotype, long and narrow leaves, with NtCESA induced and significant increase of cellulose. In conclusion, our data suggest that tomato SIMYB1/2 have transcriptional regulatory roles in cellulose biosynthesis and SIMYB2 was more effective than SIMYB1, which may due to the transcriptional activation by SIMYB2 on SIMYB1 and itself.展开更多
基金supported by the National Key Research and Development Program of China(2021YFF1000304)the National Natural Science Foundation of China(32222060)Anhui Agricultural University(RC422404)to J.Y.
文摘Mitochondria are semi-autonomous organelles present in eukaryotic cells,containing their own genome and transcriptional machinery.However,their functions are intricately linked to proteins encoded by the nuclear genome.Mitochondrial transcription termination factors(mTERFs)are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts.Despite their recognized importance,the specific roles of mTERF proteins in maize remain largely unexplored.Here,we clone and functionally characterize the maize mTERF18 gene.Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos,resulting in abortive phenotypes.Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18.We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests.mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein.Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene,leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity.Furthermore,transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects.Collectively,these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.
基金supported by grants from the National Key Research and Development Program of China(Grant Nos.2023YFD2301000,2022YFD2100102)National Natural Science Foundation of China(Grant No.32302616)+1 种基金Shandong Province(Grant No.ZR2023QC032)the Key Research and Development Program of Shandong Province(Grant No.2023CXGC010709).
文摘Chlorogenic acid(CGA),a potent antioxidant with antimicrobial,antiviral,and metabolic regulatory properties,plays multifunctional roles in apple fruit by enhancing postharvest quality,extending shelf life through oxidative stress reduction,and inhibiting enzymatic browning to preserve color,flavor,and nutritional integrity.Despite the established role of hydroxycinnamoyl transferase(HCT)as a rate-limiting enzyme in CGA biosynthesis,the specific HCT gene responsible for this process and its regulatory mechanisms remain elusive.To address this knowledge gap,we systematically investigated CGA accumulation dynamics during apple storage and functionally characterized MdHCT6,a candidate gene within the HCT family.We found that the chlorogenic acid content in apple fruit increased significantly during postharvest storage compared with the initial storage.Transcriptome analysis showed that the expression level of MdHCT6 was significantly higher than that of other HCT homologues,which was consistent with the reverse transcription quantitative PCR(RT-qPCR)results.In vitro enzymatic assays demonstrated that MdHCT6 catalyzes the synthesis of chlorogenic acid using shikimic acid and quinic acid as precursors,while genetic evidence confirmed its role as a key positive regulator of chlorogenic acid accumulation in apples.Furthermore,we identified the transcription factor MdMYB93 as a direct upstream activator of MdHCT6,establishing a regulatory cascade that governs CGA production.This work not only deciphers the molecular hierarchy of CGA biosynthesis in apples but also provides actionable targets for genetic improvement of antioxidant capacity and postharvest resilience in apple germplasm.
基金supported by the National Natural Science Foundation of China(Grant No.:62101087)the China Postdoctoral Science Foundation(Grant No.:2021MD703942)+2 种基金the Chongqing Postdoctoral Research Project Special Funding,China(Grant No.:2021XM2016)the Science Foundation of Chongqing Municipal Commission of Education,China(Grant No.:KJQN202100642)the Chongqing Natural Science Foundation,China(Grant No.:cstc2021jcyj-msxmX0834).
文摘Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.
基金Supported by the National Key R&D Program of China,No.2022YFC2503700 and No.2022YFC2503703the National Health Commission Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX005.
文摘BACKGROUND Esophageal cancer(ESCA)poses a significant challenge in oncology because of the limited treatment options and poor prognosis.Therefore,enhancing the therapeutic effects of radiotherapy for ESCA and identifying relevant therapeutic targets are crucial for improving both the survival rate and quality of life of patients.AIM To define the role of the transcription factor Snail family transcriptional repressor 1(SNAI1)in ESCA,particularly its regulation of radiosensitivity.METHODS A comprehensive analysis of TCGA data assessed SNAI1 expression in ESCA.Survival curves correlated SNAI1 levels with radiotherapy outcomes.Colony formation assays,flow cytometry,and a xenograft model were used to evaluate tumor radiosensitivity and apoptosis.Western blot validated protein expression,while Chromatin im-munoprecipitation assays examined SNAI1's role in regulating epithelial-mesenchymal transition(EMT).RESULTS SNAI1 expression in ESCA cell lines and clinical specimens emphasizes its central role in this disease.Elevated SNAI1 expression is correlated with unfavorable outcomes in radiotherapy.Downregulation of SNAI1 enhances the sensitivity of ESCA cells to ionizing radiation(IR),resulting in remarkable tumor regression upon IR treatment in vivo.This study underscores the direct involvement of SNAI1 in the regulation of EMT,particularly under IR-induced conditions.Furthermore,inhibiting deacetylation effectively suppresses EMT,suggesting a potential avenue to enhance the response to radiotherapy in ESCA.CONCLUSION This study highlights SNAI1's role in ESCA radiosensitivity,offering prognostic insights and therapeutic strategies to enhance radiotherapy by targeting SNAI1 and modulating EMT processes.
基金This work was supported by the National High Technology R&D Project of China (No.2002AA207009) and Wuhan Dawn Project for Youth (No. 20035002016-36).
文摘Northern blot analysis was conducted with mitochondrial RNA from seedling leaves, floral buds, and developing seeds of NCa CMS, maintainer line and fertile F1 using ten mitochondrial genes as probes. The results revealed that 9 out of the 10 mitochondrial genes, except for atp6, showed no difference in different tissues of the corresponding materials of NCα CMS system and that they might be constitutively expressed genes. Eight genes, such as orf139, orf222, atpl, cox1, cox2, cob, rm5S, and rm26S, showed no difference among the three tissues of all the materials detected. So the expression of these eight genes was not regulated by nuclear genes and was not tissue-specific. The transcripts of atp9 were identical among different tissues, but diverse among different materials, indicating that transcription of atp9 was neither controlled by nuclear gene nor tissue-specific. Gene atp6 displayed similar transcripts with the same size among different tissues of all the materials but differed in abundance among tissues of corresponding materials and its expression might be tissue-specific under regulation of nuclear gene. Moreover, three transcripts of orf222 were detected in the floral buds of NCa cms and fertile F1, but no transcript was detected in floral buds of the maintainer line.The transcription of orf139 was similar to that of orf222 but only two transcripts of 0.8 kb and 0.6 kb were produced. The atp9 probe detected a single transcript of 0.6 kb in NCa cms and in maintainer line and an additional transcript of 1.2 kb in fertile F1. The relationship of expression of orf222, orf139, and atp9 with NCa sterility was discussed.
基金Supported by the National“863”Program(2006AA10A210)~~
文摘The peaT1 gene fragment was amplified from pGEM-6p-l-peaT1 by PCR, and recovered target gene was cloned into pLexA vector. After digestion and sequencing, the bait vector pLexA-peaT1 was transformed into yeast strain EGY48 [p8op-lacZ] by PEG/LiAC, and the transcriptional activity of bait vector was detected. The results showed that recombinant bait plasmid pLexA-PEMG1 was constructed, for the two bands of recombinant bait plasmid in agarose gel eleetrophoresis were expected after digesting by restriction endonuclease EcoR I and Xho I. Therefore, the recombinant bait plasmid could be used in yeast two-hybrid system to screen a cDNA library.
基金the National Key Research and Development Program of China(2024YFE0102300)National Natural Science Foundation of China(32470578)to Chunli Chen+1 种基金the funding support from the Fundamental Research Funds for the Central Universities(Program No.2662023LXPY003)to Sisi LiuDr.Junli Liu from Durham University for his reviewing on the manuscript.
文摘Auxins were the first of the major plant hormones and played key roles in plant growth and development.Auxin triggered gene expression through several mechanisms.The canonical textbook model is that auxin binds to TIR1/AFB receptors and stabilizes their interaction with Aux/IAA repressors,leading to their ubiquitination and degradation,which results in activation of ARFs transcription factors.The recent study published in Nature by JiíFriml and co-authors updated the view on gene expression regulated by auxin.The role of TIR-produced cAMP was confirmed to be the second messenger in transcriptional auxin signaling.The conclusions raised in this Nature article shift the paradigm about the regulation of plant growth and development by auxin to the modulation of cAMP production and its interaction with candidate targets.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32025032 and 32202415)the Agricultural Breeding Project of Ningxia Hui Autonomous Region(Grant No.NXNYYZ20210104)the National Key Research and Development Program of China(Grant No.2022YFE0116400).
文摘In climacteric fruits,the role of ethylene in promoting ripening process and its molecular regulatory mechanisms have been well elucidated.However,research into ethylene's roles in non-climacteric fruits has only advanced in recent years,largely because these fruits produce much less ethylene than climacteric fruits.Consequently,reports on its molecular regulatory involvement are still limited.Grape(Vitis vinifera L.),one of the most economically valuable fruits,is regarded as a classical non-climacteric fruit.In this study,an enzyme participating in the last step of ethylene biosynthesis,VvACO1,has been identified as a key enzyme controlling ethylene release in grape fruits(Vitis vinifera‘Jingyan’and‘Red Balado’)using correlation analysis and enzymatic experiments.The transcriptional regulation of VvACO1 was investigated by integrating multiple methods such as DNA pull-down assays,co-expression analysis,dual luciferase reporting system,yeast one-hybrid assays,and transgenic experiments.Our findings revealed that the upregulation of VvACO1 in grape fruits was primarily caused by the removal of transcriptional inhibition.Remarkably,seven transcription factors(TFs)were identified as inhibitors of VvACO1,including VvHY5 from bZIP family,VvWIP2 from C2H2 family,VvBLH1 from Homeobox family,VvAG1 and VvCMB1 from MADS-box family,VvASIL1 and VvASIL2 from Trihelix family.These seven TFs were located in nuclei and exhibited transcriptional inhibition activity.Notably,VvAG1 and VvASIL2 could inhibit VvACO1 expression when overexpressed in grape leaves.Our findings provided theoretical clues for differences of ethylene release regulation between climacteric and non-climacteric fruits,also the identified seven TFs could be potential targets for grape molecular breeding.
基金supported by the National Natural Science Foundation of China[grant numbers 32271914 and 32301660]the Quality Engineering Project of Anhui Provincial Department of Education[grant number 2023zygzts007].
文摘Acer paxii belongs to the evergreen species of Acer,but it exhibits a unique feature of reddish leaves in fall in subtropical regions.Although the association of AP2/ERF transcription factors with color change has been well-documented in prior research,molecular investigations focusing on AP2/ERF remain notably lacking in Acer paxii.This research focuses on performing an extensive genome-wide investigation to identify and characterize the AP2/ERF gene family in Acer paxii.As a result,123 ApAP2/ERFs were obtained.Phylogenetic analyses categorized the ApAP2/ERF family members into 15 subfamilies.The evolutionary traits of the ApAP2/ERFs were investigated by analyzing their chromosomal locations,conserved proteinmotifs,and gene duplication events.Moreover,investigating gene promoters revealed their potential involvement in developmental regulation,physiological processes,and stress adaptationmechanisms.Measurements of anthocyanin content revealed a notable increase in red leaves during autumn.Utilizing transcriptome data,transcriptomic profiling revealed that the majority of AP2/ERF genes in Acer paxii displayed significant differential expression between red and green leaves during the color-changing period.Furthermore,through qRT-PCR analysis,it was found that the gene expression levels of ApERF006,ApERF014,ApERF048,ApERF097,and ApERF107 were significantly elevated in red leaves.This indicates their potential participation in leaf pigmentation processes.These findings offer significant insights into the biological significance of ApAP2/ERF transcription factors and lay the groundwork for subsequent investigations into their regulatorymechanisms underlying leaf pigmentation in Acer paxii.
基金funded by the National Key R&D Program of China(2023YFD1401401)the China Agriculture Research System(CARS27)。
文摘Defensin,an essential component of plant development,is indispensable in pathogen resistance.However,the molecular function of defensins under pathological conditions of Cytospora canker has not been characterized in apple plants.The present study exhibits a detailed overview of the phylogeny and structure of 29 defensins(MdDEF)in apple.Expression analysis revealed that MdDEF genes were spatiotemporally diverse across apple tissues.Five MdDEF genes were found to be significantly up-regulated following a challenge with Cytospora mali.The transgenic overexpression of five defensin genes in apple calli enhanced resistance to C.mali.Among them,MdDEF30 was strongly induced and conferred the highest resistance level in vivo.Meanwhile,antifungal activity assays in vitro demonstrated that a recombinant protein produced from MdDEF30could inhibit the growth of C.mali.Notably,MdDEF30 promoted the accumulation of reactive oxygen species(ROS)and activated defense-related genes such as PR4,PR10,CML13,and MPK3.Co-expression regulatory network analysis showed that MdWRKY75 may regulate the expression of MdDEF30.Further yeast onehybrid(Y1H),luciferase,and chromatin Immunoprecipitation quantitative polymerase chain reaction(ChIPqPCR)assays verified that MdWRKY75 could directly bind to the promoter of MdDEF30.Importantly,pathogen inoculation assays confirmed that MdWRKY75 positively regulates resistance by transcriptionally activating MdDEF30.Overall,these results demonstrated that MdDEF30 promotes resistance to C.mali in apple plants and that MdWRKY75 regulates MdDEF30 expression during the induction of resistance,thereby clarifying biochemical mechanisms of resistance to C.mali in apple trees.
文摘Since transgene silencing was found in transgenic plants,many scholars have studied it extensively and considered that it has three functional mechanisms:post dependent gene silencing,transcriptional gene silencing,post transcriptional gene silencing.At the moment,people have mainly focused on the study of post transcriptional gene silencing and found its features:extensivity,conduction and peculiarity,also put forward some hypothesis for its mechanisms,for example,RNA threshold model,aberrant RNA model,inter or intra molecular base pairing model and so on.Furthermore,post transcriptional gene silencing is being applied in gene engineering of plants.Recently the people have found that post transcriptional gene silencing has bearing on capacity plants resisting virus.Many researchers have studied post transcriptional gene silencing,but there are some questions which need be solved in the future.This article summarizes progresses in features,mechanisms,applies of post transcriptional gene silencing about transgenic plants.
文摘While human immunodeficiency virus 1(HIV-1) infectionis controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference(RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by noncoding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing(TGS), as well as finetuning their expression through post-transcriptional gene silencing(PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.
文摘As part of our efforts to identify novel contraceptive targets in the epididymis we performed transcriptional profiling on each of the 10 and 19 segments of the mouse and rat epididymidis, respectively, using Affymetrix whole genome microarrays. A total of 17 096 and 16 360 probe sets representing transcripts were identified as being expressed in the segmented mouse and rat epididymal transcriptomes, respectively. Comparison of the expressed murine transcripts against a mouse transcriptional profiling database derived from 22 other mouse tissues identified 77 transcripts that were expressed uniquely in the epididymis. The expression of these genes was further evaluated by reverse transcription polymerase chain reaction （RT-PCR） analysis of RNA from 21 mouse tissues. RT-PCR analysis confirmed epididymis-specific expression of Defensin Beta 13 and identified two additional genes with expression restricted only to the epididymis and testis. Comparison of the 16 360 expressed transcripts in the rat epididymis with data of 21 other tissues from a rat transcriptional profiling database identified 110 transcripts specific for the epididymis. Sixty-two of these transcripts were further investigated by qPCR analysis. Only Defensin 22 （E3 epididymal protein） was shown to be completely specific for the epididymis. In addition, 14 transcripts showed more than 100-fold selective expression in the epididymis. The products of these genes might play important roles in epididymal and/or sperm function and further investigation and validation as contraceptive targets are warranted. The results of the studies described in this report are available at the Mammalian Reproductive Genetics （MRG） Database （http：//mrg. genetics.washington.edu/）. （Asian J Androl 2007July; 9： 522-527）
基金supported by the National Natural Science Foundation of China (31871634, 31500985)
文摘Retrotransposons account for a large proportion of the genome and genomic variation, and play key roles in creating novel genes and diversifying the genome in many eukaryotic species. Although retrotransposons are abundant in plants, their roles had been underestimated because of a lack of research. Here, we characterized a gibberellin Acid (GA)-insensitive dwarf mutant, 84133, in foxtail millet. Map-based cloning revealed a 5.5-kb Copia-like retrotransposon insertion in DWARF1 (D1), which encodes a DELLA protein. Transcriptional analysis showed that the Copia retrotransposon mediated the transcriptional reprogramming of D1 leading to a novel N-terminal-deleted truncated DELLA transcript that was putatively driven by Copia's LTR, namely D1-TT, and another chimeric transcript. The presence of D1-TT was confirmed by protein immunodetection analysis. Furthermore, D1-TT protein was resistant to GA3 treatment compared with the intact DELLA protein due to its inability to interact with the GA receptor, SiGID1. Overexpression of D1-TT in foxtail millet resulted in dwarf plants, confirming that it determines the dwarfism of 84133. Thus, our study documents a rare instance of long terminal repeat (LTR) retrotransposon-mediated transcriptional reprograming in the plant kingdom. These results shed light on the function of LTR retrotransposons in generating new gene functions and genetic diversity.
基金the National Natural Science Foundation of China(grant Nos.31801601,31925035,and 31871855)the China Postdoctoral Science Foundation(2018T110153)the Youth Innovation Promotion Association CAS(2019083).
文摘Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELONGATED HYPOCOTYL 5(HY5),a master regulator in the light signaling pathway,is required for normal fruit ripening in tomato(Solanum lycopersicum).Loss of function of tomato HY5(SlHY5)impairs pigment accumulation and ethylene biosynthesis.Transcriptome profiling identified 2948 differentially expressed genes,which included 1424 downregulated and 1524 upregulated genes,in the Slhy5 mutants.In addition,genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation.Surprisingly,the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants,and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins.Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes.These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery.Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.
文摘Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclero- sis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atheroscle- rotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.
基金supported by grants from the Ministry of Agriculture of China (Nos.2008ZX08003-003 and 2009ZX08003-023B)Shandong Agricultural University (No.23651)
文摘Starch biosynthesis is important during endosperm development. Much has been known for the regulation of gene expression involved in starch synthesis, less information is available on the genome-wide expression profiles as a consequence of impaired starch synthesis. In this study, we examined the transcriptional responses through microarray analysis in an ae wx double-mutant with loss-of-function starch branching enzyme IIb （SBEIIb） and granule-bound starch synthase I （GBSSI）. Through Gene Ontology enrichment analysis, we identified differentially expressed genes （DEGs） involved in chromatin organization and lipid transport. The DEGs also include alcohol dehydrogenase genes and pyruvate decarboxylase genes involved in sugar metabolism. In summary, the ae wx double mutations caused pleiotropic effects and transcriptional changes for a number of genes involved in metabolism, cellular response and organization. Therefore, a block in starch synthesis triggers transcriptional responses to favour the flux of excess carbohydrates into glycolysis, pentose phosphate pathway, and cell wall biosynthesis, but not toward the synthesis of alternative storage compounds.
文摘Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.
基金supported by National Natural Science Foundation of China (81670874, 81500354, and 81772999)Shenzhen Science Foundation (JCYJ20160308104109234)
文摘Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.
基金supported by the International Science & Technology Cooperation Program of China (2011DFB31580)the National Basic Research Program of China (2013CB127104)the Natural Science Foundation of Zhejiang Province,China (LR16C150001)
文摘Cellulose, a major constituent of plant biomass, is synthesized by a cellulose synthase complex. It has been demonstrated that MYB genes transcriptionally regulate cellulose synthase in Arabidopsis. However, little is known about this process in tomato. Here, two MYB （SIMYB1/2） and three cellulose synthase （CESA） （SICESA41516） genes were isolated. SIMYB1/2 and SICESA4/5/6 accumulation was found to correspond to cellulose accumulation in different tissues of tomato. Dual luciferase assays indicated that these two MYBs were transcriptional activators that interact with promoters of SICESA4/5/6. Moreover, SIMYB2 could also activate promoters of SIMYB1/2, suggesting the possible underlying auto-activation mech- anisms for MYB transcription factors. Transient over-expression of SlMYB1/2 in Nicotiana tabacum up-regulated tobacco endogenous NtCESA genes and increased cellulose accumulation. The function of SIMYB112 was further investigated using stable transformation and the results indicated that N. tabacum lines heterologous expressing SIMYB1/2 displayed a pleiotropic phenotype, long and narrow leaves, with NtCESA induced and significant increase of cellulose. In conclusion, our data suggest that tomato SIMYB1/2 have transcriptional regulatory roles in cellulose biosynthesis and SIMYB2 was more effective than SIMYB1, which may due to the transcriptional activation by SIMYB2 on SIMYB1 and itself.
