LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclatur...LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.展开更多
Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes su...Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-γ expression. In order to achieve proper IFN-γ-mediated immunological effects, IFN-γ expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-γ expression by Prospero-related Homeobox （Proxl）. In Jurkat T cells and primary human CD4＋ T cells, Proxl expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-γ expression. Reporter analysis and chromatin immunoprecipitation （CHIP） revealed that Proxl associates with and inhibits the transcription activity of IFN-γ promoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Proxl and the nuclear receptor peroxisome proliferator-activated receptor gamma （PPARγ）, which is also an IFN-γ repressor in T cells. By introducing deletions and mutations into Proxl, we show that the repression of IFN-γ promoter by Proxl is largely dependent upon the physical interaction between Proxl and PPARγ. Furthermore, PPARγ antagonist treatment removes Proxl from IFN-γ promoter and attenuates repression of IFN-γ expression by Proxl. These findings establish Proxl as a new negative regulator of IFN-γ expression in T cells and will aid in the understanding of IFN-γ transcription regulation mechanisms.展开更多
Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were establish...Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were established by in-fection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells. Results Western blot results showed that EZH2 protein level increased upon SIRT1 de-pletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter region of EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases. Conclusions Depletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expres-sion.展开更多
As a genre that expressed women＇s dark protests, fantasies and the fear, female Gothic was not theorized until the late 1960s, and before its theorization, this convention was adopted by many women writers in their w...As a genre that expressed women＇s dark protests, fantasies and the fear, female Gothic was not theorized until the late 1960s, and before its theorization, this convention was adopted by many women writers in their works. Charlotte Perkins Gilman＇s The yellow wallpaper is one of the many examples. As the epitome of female gothic, The yellow wallpaper utilized the female gothic conventions--the grotesque symbol of yellow wallpaper, the hysteric narrative format and the archetype image of madwoman, to express women＇s status of her time--their repression, rebellion and quest for the ＂true self＂.展开更多
This paper carries out empirical analysis of the ration behavior of rural credit cooperatives in less developed regions in providing loan services to rural households. It also inspects the interaction between rural ho...This paper carries out empirical analysis of the ration behavior of rural credit cooperatives in less developed regions in providing loan services to rural households. It also inspects the interaction between rural households＇ demand for credit and the loan supply from rural credit cooperatives with simultaneous discrete model. The performance of supporting agriculture through a new round reform of rural credit cooperatives is doubtable in this sample region.展开更多
The pollen exine,an inert lipid layer,is the outermost layer of the pollen wall and mainly consists of sporopollenin[1,2].Normal exine contributes to male fertility and geometric patterns of pollen grain[[1],[2],[3]]....The pollen exine,an inert lipid layer,is the outermost layer of the pollen wall and mainly consists of sporopollenin[1,2].Normal exine contributes to male fertility and geometric patterns of pollen grain[[1],[2],[3]].Genetic and physicochemical processes control exine formation and genic male sterility(GMS)genes constitute a significant proportion of identified genetic factors[[1],[2],[3],[4]].To date,more than 200 GMS genes have been identified in plants[4,5].The precise molecular mechanisms underlying exine formation rely on genetic networks established by these GMS genes.However,the specific genetic networks underlying the exine formation remain unclear.展开更多
Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates.However,the neural mechanisms of coding the similarity of diffe...Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates.However,the neural mechanisms of coding the similarity of different individuals’bodies of the same species to support their categorical representations remain unclear.Using electroencephalography(EEG)and magnetoencephalography(MEG),we investigated the temporal and spatial characteristics of neural processes shared by different individual body silhouettes of the same species by quantifying the repetition suppression of neural responses to human and animal(chimpanzee,dog,and bird)body silhouettes showing different postures.Our EEG results revealed significant repetition suppression of the amplitudes of early frontal/central activity at 180–220 ms(P2)and late occipitoparietal activity at 220–320 ms(P270)in response to animal(but not human)body silhouettes of the same species.Our MEG results further localized the repetition suppression effect related to animal body silhouettes in the left supramarginal gyrus and left frontal cortex at 200–440 ms after stimulus onset.Our findings suggest two neural processes that are involved in spontaneous categorical representations of animal body silhouettes as a cognitive basis of human-animal interactions.展开更多
Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cel...Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cells.Therefore,exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.Method:This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive(ER^(+))breast cancer.We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions.ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites.To validate the ChIP-seq results,qChIP,western blotting,and quantitative polymerase chain reaction(qPCR)were performed.Through TUNEL assay,cell counting assay,colony formation assay,and the mouse xenograft models,the effect of FOXK1 on breast cancer progression was detected.Finally,by analyzing online databases,the correlation between FOXK1 and the survival of breast cancer patients was examined.Results:FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway.Abnormally high expression of FOXK1 prevents the apoptosis of ER+breast cancer cells in vitro and promotes ER+breast tumor progression in vivo.Furthermore,the expression of FOXK1 is negatively correlated with the survival of ER+breast cancer patients.Conclusion:FOXK1 promotes ER+breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+breast cancer treatment.展开更多
Gibberellic acid （GA） regulates many aspects of plant growth and development. The DELLA proteins act to restrain plant growth, and GA relieves this repression by promoting their degradation via the 26S proteasome pa...Gibberellic acid （GA） regulates many aspects of plant growth and development. The DELLA proteins act to restrain plant growth, and GA relieves this repression by promoting their degradation via the 26S proteasome pathway. The elucidation of the crystalline structure of the GA soluble receptor GID1 protein represents an important breakthrough for understanding the way in which GA is perceived and how it induces the destabilization of the DELLA proteins. Recent advances have revealed that the DELLA proteins are involved in protein-protein interactions within various environmental and hormone signaling pathways. In this review, we highlight our current understanding of the ＇relief of repression＇ model that aims to explain the role of GA and the function of the DELLA proteins, incorporating the many aspects of cross-talk shown to exist in the control of plant development and the response to stress.展开更多
Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin stru...Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin structure and is associated with gene activation, whereas deacetylation of histone is often correlated with ＇closed＇ chromatin and gene repression. Histone deacetylation is catalyzed by histone deacetylases （HDACs）. A growing number of studies have demonstrated the importance of histone deacetylation/acetylation on genome stability, transcriptional regulation, and development in plants. Furthermore, HDACs were shown to interact with various chromatin remolding factors and transcription factors involved in transcriptional repression in multiple developmental processes. In this review, we summarized recent findings on the transcriptional repression mediated by HDACs in plants.展开更多
Instability in the worm dollar standard, as most recently manifested in the US Federal Reserve＇s near-zero interest rate policy, has caused consternation in emerging markets with naturally higher interest rates. Chin...Instability in the worm dollar standard, as most recently manifested in the US Federal Reserve＇s near-zero interest rate policy, has caused consternation in emerging markets with naturally higher interest rates. China has been provoked into speeding RMB ＂internationalization ＂; that is, opening up domestic financial markets to reduce its dependence on the US dollar for invoicing trade and making international payments. However, despite rapid percentage growth in offshore financial markets in RMB, the Chinese authorities are essentially trapped into maintaining exchange controls （reinforced by financial repression in domestic interest rates） to avoid an avalanche of foreign capital inflows that would threaten inflation and asset price bubbles by driving nominal interest rates on RMB assets down further. Because a floating （appreciating） exchange rate could attract even more hot money inflows, the People＇s Bank of China should focus on keeping the yuan/dollar rate stable so as to encourage naturally high wage increases to help balance China ＂s international competitiveness. However, further internationalization of the RMB, as with the proposed Shanghai pilot free trade zone, is best deferred until world interest rates rise to more normal levels.展开更多
This paper attempts to explain why sterilized intervention was so successful and sustainable in China during the first decade of the 21st century. We argue that the Chinese Government established a sterilization cost-...This paper attempts to explain why sterilized intervention was so successful and sustainable in China during the first decade of the 21st century. We argue that the Chinese Government established a sterilization cost-sharing mechanism among the Peoples Bank of China, commercial banks and the househoM sector. On the one hand, Chinese commercial banks have to assume some of the sterilization costs bypurchasing low yield central bank bills and maintaining high levels of required reserves. On the other hand, Chinese households assume some of the sterilization costs by bearing negative real deposit interest rates. The cost- sharing mechanism under financial repression prevents a huge quasi-fiscal loss by the Peoples Bank of China as well as high inflation. However, Chinese households have become victims of this financial repression. Faced with the pressure of changing the growth model from investment-driven to domestic consumption-driven, the interest rate will have to be liberalized eventually, which will, in turn, make sterilized intervention unsustainable.展开更多
From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which Pe...From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which PeG machinery mediates gene repression is still largely unknown in plants. Compared to animals, few PcG proteins have been identi- fied in plants, not only because just some of these proteins are clearly conserved to their animal counterparts, but also because some PcG functions are carried out by plant-specific proteins, most of them as yet uncharacterized. For a long time, the apparent lack of Polycomb Repressive Complex （PRC）I components in plants was interpreted according to the idea that plants, as sessile organisms, do not need a long-term repression, as they must be able to respond rapidly to environmental signals; however, some PRC1 components have been recently identified, indicating that this may not be the case. Furthermore, new data regarding the recruitment of PcG complexes and maintenance of PcG repression in plants have revealed important differences to what has been reported so far. This review highlights recent progress in plant PcG function, focusing on the role of the putative PRC1 components.展开更多
Tissue formation, the identity of cells, and the functions they fulfill, are results of gene regulation. The male gametophyte of plants, pollen, is outstanding in this respect as several hundred genes expressed in pol...Tissue formation, the identity of cells, and the functions they fulfill, are results of gene regulation. The male gametophyte of plants, pollen, is outstanding in this respect as several hundred genes expressed in pollen are not expressed in the sporophyte. How pollen-specific genes are down-regulated in the sporophyte has yet to be established. In this study, we have performed a bioinformatics analysis of publicly available genome-wide epigenetics data of sev- eral sporophytic tissues. By combining this analysis with DNase ! footprinting data, we assessed means by which the repression of pollen-specific genes in the Arabidopsis sporophyte is conferred. Our findings show that, in seedlings, the majority of pollen-specific genes are associated with histone-3 marked by mono- or trimethylation of Lys-27 （H3K27me1/ H3K27me3）, both of which are repressive markers for gene expression in the sporophyte. Analysis of DNase footprint profiles of pollen-specific genes in the sporophyte displayed closed chromatin proximal to the start codon. We describe a model of two-staged gene regulation in which a lack of nucleosome-free regions in promoters and histone modifications in open reading frames repress pollen-specific genes in the sporophyte.展开更多
Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon s...Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon sources is available,CCR,a global regulatory mechanism,inhibits the expression and activity of cellular processes associated with utilization of secondary carbon sources in the presence of the preferred carbon source.CCR is known to be executed by completely different mechanisms in different bacteria,yeast,and fungi.In addition to regulating catabolic genes,CCR also appears to play a key role in the expression of genes involved in plant–microbe interactions.Here,we present a detailed overview of CCR mechanisms in various bacteria.We highlight the role of CCR in beneficial as well as deleterious plant–microbe interactions based on the available literature.In addition,we explore the global distribution of known regulatory mechanisms within bacterial genomes retrieved from public repositories and within metatranscriptomes obtained from different plant rhizospheres.By integrating the available literature and performing targeted meta-analyses,we argue that CCR-regulated substrate use preferences of microorganisms should be considered an important trait involved in prevailing plant–microbe interactions.展开更多
It is generally believed that physical heterogeneity in common resource or evolutionary restraint can sufficiently prevent direct conflict between host and symbionts in mutualism systems. Our data on fig/fig wasp reci...It is generally believed that physical heterogeneity in common resource or evolutionary restraint can sufficiently prevent direct conflict between host and symbionts in mutualism systems. Our data on fig/fig wasp reciprocal mutualism(Ficus racemosa), however, show that structural barriers of female flowers or genetic constraints of pollinators previously hypothesized exist, but cannot sufficiently maintain the mutualism stability. The results show that a positive relationship between seed and wasp production could be maintained in warm season, which might be because of density dependence restraint among foundresses and their low oviposition and pollination efficiency, keeping common resource(female flowers) utilization unsaturated. Whilst, a negative correlation between wasp offspring and viable seed production was also observed in cold season, which might be that the increased oviposition and pollination efficiency maximized the common resource utilization. The fitness trade-off between fig and pollinator wasps is greatly affected by environmental or ecological variations. The local stability might result from temporal low exploitation efficiency of pollinators together with interference competition among pollinators. We suggest that host repression through the active regulation of bract closure, which can create interference competition among the foundresses and prevent extra more foundresses sequential entry in fruit cavities, would help the figs avoiding the cost of over-exploitation. This essentially takes the same role as sanctioning of cheating or competitive behaviors.展开更多
Translational repression is a conserved mechanism in microRNA(miRNA)-guided gene silencing.In Arabidopsis,ARGONAUTE1(AGO1),the major miRNA effector,localizes in the cytoplasm for mRNA cleavage and at the endoplasmic r...Translational repression is a conserved mechanism in microRNA(miRNA)-guided gene silencing.In Arabidopsis,ARGONAUTE1(AGO1),the major miRNA effector,localizes in the cytoplasm for mRNA cleavage and at the endoplasmic reticulum(ER)for translational repression of target genes.However,the mechanism underlying miRNA-mediated translational repression is poorly understood.In particular,how the subcellular partitioning of AGO1 is regulated is largely unexplored.Here,we show that the plant hormone brassinosteroids(BRs)inhibit miRNA-mediated translational repression by negatively regulating the distribution of AGO1 at the ER in Arabidopsis thaliana.We show that the protein levels rather than the transcript levels of miRNA target genes were reduced in BR-deficient mutants but increased under BR treatments.The localization of AGO1 at the ER was significantly decreased under BR treatments while it was increased in the BR-deficient mutants.Moreover,ROTUNDIFOLIA3(ROT3),an enzyme involved in BR biosynthesis,co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner.Complementation analysis showed that the AGO1-ROT3 interaction is necessary for the function of ROT3.Our findings provide new clues to understand how miRNA-mediated gene silencing is regulated by plant endogenous hormones.展开更多
Carbon catabolite repression(CCR),which is mainly mediated by Cre1 and triggered by glucose,leads to a decrease in cellulase production in Trichoderma reesei.Many studies have focused on modifying Cre1 for alleviating...Carbon catabolite repression(CCR),which is mainly mediated by Cre1 and triggered by glucose,leads to a decrease in cellulase production in Trichoderma reesei.Many studies have focused on modifying Cre1 for alleviating CCR.Based on the homologous alignment of CreA from wild-type Penicillium oxalicum 114–2(Po-0)and cellulase hyperproducer JUA10-1(Po-1),we constructed a C-terminus substitution strain—Po-2—with decreased transcriptional levels of cellulase and enhanced CCR.Results revealed that the C-terminal domain of CreAPo−1 plays an important role in alleviating CCR.Furthermore,we replaced the C-terminus of Cre1 with that of CreAPo−1 in T.reesei(Tr-0)and generated Tr-1.As a control,the C-terminus of Cre1 was truncated and Tr-2 was generated.The transcriptional profiles of these transformants revealed that the C-terminal chimera greatly improves cellulase transcription in the presence of glucose and thus upregulates cellulase in the presence of glucose and weakens CCR,consistent with truncating the C-terminus of Cre1 in Tr-0.Therefore,we propose constructing a C-terminal chimera as a new strategy to improve cellulase production and alleviate CCR in the presence of glucose.展开更多
Under near-zero US interest rates, the international dollar standard malfunctions. Emerging markets with naturally higher interest rates are swamped with hot money inflows. Emerging market central banks intervene to p...Under near-zero US interest rates, the international dollar standard malfunctions. Emerging markets with naturally higher interest rates are swamped with hot money inflows. Emerging market central banks intervene to prevent their currencies from rising precipitately. They lose monetary control and domestic prices begin inflating. Primary commodity prices rise worldwide unless interrupted by an international banking crisis＇. This cyclical inflation on the dollar＇s periphery only registers in the US core eonsumer price index with a long lag. The zero interest rate policy also fails to stimulate the US economy as domestic finaneial intermediation by banks and money market mutual funds is repressed. Because China is forced to keep its interest rates below market-clearing levels, it also suffers from finaneial repression, although in a form differing from that in the USA.展开更多
基金We thank Dr Ramin Shiekhattar （Wistar Institute, USA） for the baculoviruses expressing Flag-LSD1 and Drs Jianguo Song and Degui Chen （Shanghai Institute of Biochemistry and Cell Biol- ogy, China） for anti-HDAC1 antibody and H3K36me2 antibody, respectively. This study was partially supported by grants from the National Natural Science Foundation of China （90919025, 30871381）, the Ministry of Science and Technology of China （2009CB918402, 2009CB825601） and the Research Platform for Cell Signaling Networks from the Science and Technology Com- mission of Shanghai Municipality （06DZ22923）.
文摘LSD1 （KDM1 under the new nomenclature） was the first identified lysine-specific histone demethylase belonging to the flavin-dependent amine oxidase family. Here, we report that AOF1 （KDM1B under the new nomenclature）, a mammalian protein related to LSD1, also possesses histone demethylase activity with specificity for H3K4mel and H3K4me2. Like LSD1, the highly conserved SWIRM domain is required for its enzymatic activity. However, AOF1 differs from LSD1 in several aspects. First, AOF1 does not appear to form stable protein complexes containing histone deacetylases. Second, AOF1 is found to localize to chromosomes during the mitotic phase of the cell cycle, whereas LSD1 does not. Third, AOF1 represses transcription when tethered to DNA and this repression activity is independent of its demethylase activity. Structural and functional analyses identified its unique N-terminal Zf-CW domain as essential for the demethylase activity-independent repression function. Collectively, our study identifies AOF1 as the second histone demethylase in the family of flavin-dependent amine oxidases and reveals a demethylase-independent repression function of AOF1.
文摘Interferon-gamma （IFN-γ） is a major proinflammatory effector and regulatory cytokine produced by activated T cells and NK cells. IFN-γ has been shown to play pivotal roles in fundamental immunological processes such as inflammatory reactions, cell-mediated immunity and autoimmunity. A variety of human disorders have now been linked to irregular IFN-γ expression. In order to achieve proper IFN-γ-mediated immunological effects, IFN-γ expression in T cells is subject to both positive and negative regulation. In this study, we report for the first time the negative regulation of IFN-γ expression by Prospero-related Homeobox （Proxl）. In Jurkat T cells and primary human CD4＋ T cells, Proxl expression decreases quickly upon T cell activation, concurrent with a dramatic increase in IFN-γ expression. Reporter analysis and chromatin immunoprecipitation （CHIP） revealed that Proxl associates with and inhibits the transcription activity of IFN-γ promoter in activated Jurkat T cells. Co-immunoprecipitation and GST pull-down assay demonstrated a direct binding between Proxl and the nuclear receptor peroxisome proliferator-activated receptor gamma （PPARγ）, which is also an IFN-γ repressor in T cells. By introducing deletions and mutations into Proxl, we show that the repression of IFN-γ promoter by Proxl is largely dependent upon the physical interaction between Proxl and PPARγ. Furthermore, PPARγ antagonist treatment removes Proxl from IFN-γ promoter and attenuates repression of IFN-γ expression by Proxl. These findings establish Proxl as a new negative regulator of IFN-γ expression in T cells and will aid in the understanding of IFN-γ transcription regulation mechanisms.
基金Supported by National Natural Science Foundation of China (30721063)National Basic Research Program of China (973 Program) (2005CB522402, 2006CB910403)+1 种基金National Laboratory of Medical Molecular Biology grant (2060204)Beijing municipal government grant (YB20081002301)
文摘Objective To study the regulatory roles of SIRT1 on EZH2 expression and the further ef-fects on EZH2's repression of target gene expression. Methods The stable SIRT1 RNAi and Control RNAi HeLa cells were established by in-fection with retroviruses expressing shSIRT1 and shLuc respectively followed by puromycin selection. EZH2 protein level was detected by Western blot in either whole cell lysate or the fractional cell extract. Reverse transcription-polymerase chain reaction was performed to detect the mRNA level of EZH2. Cycloheximide was used to treat SIRT1 RNAi and Control RNAi cells for protein stability assay. Chromatin immunoprecipitation (ChIP) assay was applied to measure enrichment of SIRT1, EZH2, and trimethylated H3K27 (H3K27me3) at SATB1 promoter in SIRT1 RNAi and Control RNAi cells. Results Western blot results showed that EZH2 protein level increased upon SIRT1 de-pletion. Fractional extraction results showed unchanged cytoplasmic fraction and increased chromatin fraction of EZH2 protein in SIRT1 RNAi cells. The mRNA level of EZH2 was not affected by knockdown of SIRT1. SIRT1 recruitment was not detected at the promoter region of EZH2 gene locus. The protein stability assay showed that the protein stability of EZH2 increases upon SIRT1 knockdown. Upon SIRT1 depletion, EZH2 and H3K27me3 recruitment at SATB1 promoter increases and the mRNA level of SATB1 decreases. Conclusions Depletion of SIRT1 increases the protein stability of EZH2. The regulation of EZH2 protein level by SIRT1 affects the repressive effects of EZH2 on the target gene expres-sion.
文摘As a genre that expressed women＇s dark protests, fantasies and the fear, female Gothic was not theorized until the late 1960s, and before its theorization, this convention was adopted by many women writers in their works. Charlotte Perkins Gilman＇s The yellow wallpaper is one of the many examples. As the epitome of female gothic, The yellow wallpaper utilized the female gothic conventions--the grotesque symbol of yellow wallpaper, the hysteric narrative format and the archetype image of madwoman, to express women＇s status of her time--their repression, rebellion and quest for the ＂true self＂.
文摘This paper carries out empirical analysis of the ration behavior of rural credit cooperatives in less developed regions in providing loan services to rural households. It also inspects the interaction between rural households＇ demand for credit and the loan supply from rural credit cooperatives with simultaneous discrete model. The performance of supporting agriculture through a new round reform of rural credit cooperatives is doubtable in this sample region.
基金supported by the National Key Research and Development Program of China(2022YFF1003501 and 2023ZD04076)the National Natural Science Foundation of China(32330076 and 32301886)the Beijing Innovation Consortium of Agriculture Research System(BAIC02-2024).
文摘The pollen exine,an inert lipid layer,is the outermost layer of the pollen wall and mainly consists of sporopollenin[1,2].Normal exine contributes to male fertility and geometric patterns of pollen grain[[1],[2],[3]].Genetic and physicochemical processes control exine formation and genic male sterility(GMS)genes constitute a significant proportion of identified genetic factors[[1],[2],[3],[4]].To date,more than 200 GMS genes have been identified in plants[4,5].The precise molecular mechanisms underlying exine formation rely on genetic networks established by these GMS genes.However,the specific genetic networks underlying the exine formation remain unclear.
基金supported by the National Natural Science Foundation of China(32230043 and 32371092)the Ministry of Science and Technology of China(2019YFA0707103)+1 种基金Das Chinesisch-Deutsche Zentrum für Wissenschaftsförderung(M-0093)the High-performance Computing Platform of Peking University.
文摘Neural activities differentiating bodies versus non-body stimuli have been identified in the occipitotemporal cortex of both humans and nonhuman primates.However,the neural mechanisms of coding the similarity of different individuals’bodies of the same species to support their categorical representations remain unclear.Using electroencephalography(EEG)and magnetoencephalography(MEG),we investigated the temporal and spatial characteristics of neural processes shared by different individual body silhouettes of the same species by quantifying the repetition suppression of neural responses to human and animal(chimpanzee,dog,and bird)body silhouettes showing different postures.Our EEG results revealed significant repetition suppression of the amplitudes of early frontal/central activity at 180–220 ms(P2)and late occipitoparietal activity at 220–320 ms(P270)in response to animal(but not human)body silhouettes of the same species.Our MEG results further localized the repetition suppression effect related to animal body silhouettes in the left supramarginal gyrus and left frontal cortex at 200–440 ms after stimulus onset.Our findings suggest two neural processes that are involved in spontaneous categorical representations of animal body silhouettes as a cognitive basis of human-animal interactions.
基金Beijing High-Level Innovation and Entrepreneurship Talent Support Plan,Grant/Award Number:G04070024National Natural Science Foundation of China,Grant/Award Number:82073122。
文摘Background:Globally,breast cancer constitutes the predominant malignancy in women.Abnormal regulation of epigenetic factors plays a key role in the development of tumors.Anti-apoptosis is a characteristic of tumor cells.Therefore,exploring and identifying relevant epigenetic factors that regulate the apoptosis of tumor cells is the foundation for clarifying the pathogenesis of tumors and achieving precision antitumor therapy.Method:This study focused on exploring the epigenetic mechanism of FOXK1 in the development of estrogen receptor-positive(ER^(+))breast cancer.We used overexpressing FLAG-FOXK1 MCF-7 cells to perform silver staining mass spectrometry analysis and conducted Co-IP experiments to verify the interactions.ChIP-seq was conducted on MCF-7 cells to examine FOXK1's binding across the genome and its transcriptional target sites.To validate the ChIP-seq results,qChIP,western blotting,and quantitative polymerase chain reaction(qPCR)were performed.Through TUNEL assay,cell counting assay,colony formation assay,and the mouse xenograft models,the effect of FOXK1 on breast cancer progression was detected.Finally,by analyzing online databases,the correlation between FOXK1 and the survival of breast cancer patients was examined.Results:FOXK1 interacts with the REST/CoREST transcriptional corepression complex to transcriptionally inhibit target genes representing the apoptotic pathway.Abnormally high expression of FOXK1 prevents the apoptosis of ER+breast cancer cells in vitro and promotes ER+breast tumor progression in vivo.Furthermore,the expression of FOXK1 is negatively correlated with the survival of ER+breast cancer patients.Conclusion:FOXK1 promotes ER+breast carcinogenesis through anti-apoptosis and acts as a potential target for ER+breast cancer treatment.
文摘Gibberellic acid （GA） regulates many aspects of plant growth and development. The DELLA proteins act to restrain plant growth, and GA relieves this repression by promoting their degradation via the 26S proteasome pathway. The elucidation of the crystalline structure of the GA soluble receptor GID1 protein represents an important breakthrough for understanding the way in which GA is perceived and how it induces the destabilization of the DELLA proteins. Recent advances have revealed that the DELLA proteins are involved in protein-protein interactions within various environmental and hormone signaling pathways. In this review, we highlight our current understanding of the ＇relief of repression＇ model that aims to explain the role of GA and the function of the DELLA proteins, incorporating the many aspects of cross-talk shown to exist in the control of plant development and the response to stress.
文摘Reversible histone acetylation and deacetylation at the N-terminus of histone tails play crucial roles in regulation of eukaryotic gene activity. Acetylation of core histones usually induces an ＇open＇ chromatin structure and is associated with gene activation, whereas deacetylation of histone is often correlated with ＇closed＇ chromatin and gene repression. Histone deacetylation is catalyzed by histone deacetylases （HDACs）. A growing number of studies have demonstrated the importance of histone deacetylation/acetylation on genome stability, transcriptional regulation, and development in plants. Furthermore, HDACs were shown to interact with various chromatin remolding factors and transcription factors involved in transcriptional repression in multiple developmental processes. In this review, we summarized recent findings on the transcriptional repression mediated by HDACs in plants.
文摘Instability in the worm dollar standard, as most recently manifested in the US Federal Reserve＇s near-zero interest rate policy, has caused consternation in emerging markets with naturally higher interest rates. China has been provoked into speeding RMB ＂internationalization ＂; that is, opening up domestic financial markets to reduce its dependence on the US dollar for invoicing trade and making international payments. However, despite rapid percentage growth in offshore financial markets in RMB, the Chinese authorities are essentially trapped into maintaining exchange controls （reinforced by financial repression in domestic interest rates） to avoid an avalanche of foreign capital inflows that would threaten inflation and asset price bubbles by driving nominal interest rates on RMB assets down further. Because a floating （appreciating） exchange rate could attract even more hot money inflows, the People＇s Bank of China should focus on keeping the yuan/dollar rate stable so as to encourage naturally high wage increases to help balance China ＂s international competitiveness. However, further internationalization of the RMB, as with the proposed Shanghai pilot free trade zone, is best deferred until world interest rates rise to more normal levels.
基金financial support from the project "China's Short-term Capital Flows:Scale,Pulling Factors and Impacts," sponsored by the Chinese Academy of Social Sciences
文摘This paper attempts to explain why sterilized intervention was so successful and sustainable in China during the first decade of the 21st century. We argue that the Chinese Government established a sterilization cost-sharing mechanism among the Peoples Bank of China, commercial banks and the househoM sector. On the one hand, Chinese commercial banks have to assume some of the sterilization costs bypurchasing low yield central bank bills and maintaining high levels of required reserves. On the other hand, Chinese households assume some of the sterilization costs by bearing negative real deposit interest rates. The cost- sharing mechanism under financial repression prevents a huge quasi-fiscal loss by the Peoples Bank of China as well as high inflation. However, Chinese households have become victims of this financial repression. Faced with the pressure of changing the growth model from investment-driven to domestic consumption-driven, the interest rate will have to be liberalized eventually, which will, in turn, make sterilized intervention unsustainable.
文摘From mammals to plants, the Polycomb Group （PcG） machinery plays a crucial role in maintaining the repres- sion of genes that are not required in a specific differentiation status. However, the mechanism by which PeG machinery mediates gene repression is still largely unknown in plants. Compared to animals, few PcG proteins have been identi- fied in plants, not only because just some of these proteins are clearly conserved to their animal counterparts, but also because some PcG functions are carried out by plant-specific proteins, most of them as yet uncharacterized. For a long time, the apparent lack of Polycomb Repressive Complex （PRC）I components in plants was interpreted according to the idea that plants, as sessile organisms, do not need a long-term repression, as they must be able to respond rapidly to environmental signals; however, some PRC1 components have been recently identified, indicating that this may not be the case. Furthermore, new data regarding the recruitment of PcG complexes and maintenance of PcG repression in plants have revealed important differences to what has been reported so far. This review highlights recent progress in plant PcG function, focusing on the role of the putative PRC1 components.
文摘Tissue formation, the identity of cells, and the functions they fulfill, are results of gene regulation. The male gametophyte of plants, pollen, is outstanding in this respect as several hundred genes expressed in pollen are not expressed in the sporophyte. How pollen-specific genes are down-regulated in the sporophyte has yet to be established. In this study, we have performed a bioinformatics analysis of publicly available genome-wide epigenetics data of sev- eral sporophytic tissues. By combining this analysis with DNase ! footprinting data, we assessed means by which the repression of pollen-specific genes in the Arabidopsis sporophyte is conferred. Our findings show that, in seedlings, the majority of pollen-specific genes are associated with histone-3 marked by mono- or trimethylation of Lys-27 （H3K27me1/ H3K27me3）, both of which are repressive markers for gene expression in the sporophyte. Analysis of DNase footprint profiles of pollen-specific genes in the sporophyte displayed closed chromatin proximal to the start codon. We describe a model of two-staged gene regulation in which a lack of nucleosome-free regions in promoters and histone modifications in open reading frames repress pollen-specific genes in the sporophyte.
基金This work was supported by the French National Research Agency(ANR-18-CE32-0005,DIORE).
文摘Carbon catabolite repression(CCR)plays a key role in many physiological and adaptive responses in a broad range of microorganisms that are commonly associated with eukaryotic hosts.When a mixture of different carbon sources is available,CCR,a global regulatory mechanism,inhibits the expression and activity of cellular processes associated with utilization of secondary carbon sources in the presence of the preferred carbon source.CCR is known to be executed by completely different mechanisms in different bacteria,yeast,and fungi.In addition to regulating catabolic genes,CCR also appears to play a key role in the expression of genes involved in plant–microbe interactions.Here,we present a detailed overview of CCR mechanisms in various bacteria.We highlight the role of CCR in beneficial as well as deleterious plant–microbe interactions based on the available literature.In addition,we explore the global distribution of known regulatory mechanisms within bacterial genomes retrieved from public repositories and within metatranscriptomes obtained from different plant rhizospheres.By integrating the available literature and performing targeted meta-analyses,we argue that CCR-regulated substrate use preferences of microorganisms should be considered an important trait involved in prevailing plant–microbe interactions.
基金supported by the National Natural Science Foundation of China (31170408, 31270433, 31370408)the National Science Fund for Distinguished Young Scholars (31325005)+1 种基金NSFC-Yunnan United Fund (U1302267)the West Light Foundation of the Chinese Academy of Sciences
文摘It is generally believed that physical heterogeneity in common resource or evolutionary restraint can sufficiently prevent direct conflict between host and symbionts in mutualism systems. Our data on fig/fig wasp reciprocal mutualism(Ficus racemosa), however, show that structural barriers of female flowers or genetic constraints of pollinators previously hypothesized exist, but cannot sufficiently maintain the mutualism stability. The results show that a positive relationship between seed and wasp production could be maintained in warm season, which might be because of density dependence restraint among foundresses and their low oviposition and pollination efficiency, keeping common resource(female flowers) utilization unsaturated. Whilst, a negative correlation between wasp offspring and viable seed production was also observed in cold season, which might be that the increased oviposition and pollination efficiency maximized the common resource utilization. The fitness trade-off between fig and pollinator wasps is greatly affected by environmental or ecological variations. The local stability might result from temporal low exploitation efficiency of pollinators together with interference competition among pollinators. We suggest that host repression through the active regulation of bract closure, which can create interference competition among the foundresses and prevent extra more foundresses sequential entry in fruit cavities, would help the figs avoiding the cost of over-exploitation. This essentially takes the same role as sanctioning of cheating or competitive behaviors.
基金We are grateful to Professors Yijun Qi for providing the AGO1p::GFP-AGO1 seeds,Xuelu Wang for providing the 35S::BKI1-YFP seeds,Jianxiang Liu for providing the 35S::ER-mCherry plasmid,Hong Ma for providing theTOE1-Myc and mTOE1-Myc seeds,Xuemei Chen for providing the 35S::YFP-AGO1 plasmid,Shengben Li for providing the CSD2-HA and mCSD2-HA seeds,Fang Chang for providing the bri1-5 seeds,and Jinzhong Lin for providing ultracentrifuge equipment and technical guidance.This work was supported by grants of the National Natural Science Foundation of China(32025005,31830045,M-0398).
文摘Translational repression is a conserved mechanism in microRNA(miRNA)-guided gene silencing.In Arabidopsis,ARGONAUTE1(AGO1),the major miRNA effector,localizes in the cytoplasm for mRNA cleavage and at the endoplasmic reticulum(ER)for translational repression of target genes.However,the mechanism underlying miRNA-mediated translational repression is poorly understood.In particular,how the subcellular partitioning of AGO1 is regulated is largely unexplored.Here,we show that the plant hormone brassinosteroids(BRs)inhibit miRNA-mediated translational repression by negatively regulating the distribution of AGO1 at the ER in Arabidopsis thaliana.We show that the protein levels rather than the transcript levels of miRNA target genes were reduced in BR-deficient mutants but increased under BR treatments.The localization of AGO1 at the ER was significantly decreased under BR treatments while it was increased in the BR-deficient mutants.Moreover,ROTUNDIFOLIA3(ROT3),an enzyme involved in BR biosynthesis,co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner.Complementation analysis showed that the AGO1-ROT3 interaction is necessary for the function of ROT3.Our findings provide new clues to understand how miRNA-mediated gene silencing is regulated by plant endogenous hormones.
基金This work was supported by National Key R&D Program of China(No.2018YFA0901700)National Natural Science Foundation of China(No.31870785 and 31570040)+1 种基金the 111 Project(No.B16030)the State Key Laboratory of Microbial Technology Open Projects Fund.
文摘Carbon catabolite repression(CCR),which is mainly mediated by Cre1 and triggered by glucose,leads to a decrease in cellulase production in Trichoderma reesei.Many studies have focused on modifying Cre1 for alleviating CCR.Based on the homologous alignment of CreA from wild-type Penicillium oxalicum 114–2(Po-0)and cellulase hyperproducer JUA10-1(Po-1),we constructed a C-terminus substitution strain—Po-2—with decreased transcriptional levels of cellulase and enhanced CCR.Results revealed that the C-terminal domain of CreAPo−1 plays an important role in alleviating CCR.Furthermore,we replaced the C-terminus of Cre1 with that of CreAPo−1 in T.reesei(Tr-0)and generated Tr-1.As a control,the C-terminus of Cre1 was truncated and Tr-2 was generated.The transcriptional profiles of these transformants revealed that the C-terminal chimera greatly improves cellulase transcription in the presence of glucose and thus upregulates cellulase in the presence of glucose and weakens CCR,consistent with truncating the C-terminus of Cre1 in Tr-0.Therefore,we propose constructing a C-terminal chimera as a new strategy to improve cellulase production and alleviate CCR in the presence of glucose.
文摘Under near-zero US interest rates, the international dollar standard malfunctions. Emerging markets with naturally higher interest rates are swamped with hot money inflows. Emerging market central banks intervene to prevent their currencies from rising precipitately. They lose monetary control and domestic prices begin inflating. Primary commodity prices rise worldwide unless interrupted by an international banking crisis＇. This cyclical inflation on the dollar＇s periphery only registers in the US core eonsumer price index with a long lag. The zero interest rate policy also fails to stimulate the US economy as domestic finaneial intermediation by banks and money market mutual funds is repressed. Because China is forced to keep its interest rates below market-clearing levels, it also suffers from finaneial repression, although in a form differing from that in the USA.
