Chromatin modifications,including histone acetylation,play essential roles in regulating flowering.The CBP/p300 family HISTONE ACETYLTRANSFERASE 1(HAC1),which mediates histone acetylation,promotes the process of flora...Chromatin modifications,including histone acetylation,play essential roles in regulating flowering.The CBP/p300 family HISTONE ACETYLTRANSFERASE 1(HAC1),which mediates histone acetylation,promotes the process of floral transition;however,the precise mechanism remains largely unclear.Specifically,how HAC1 is involved in the flowering regulatory network and which genes are the direct targets of HAC1 during flowering regulation are still unknown.In this study,we elucidate the critical function of HAC1 in promoting flowering via exerting active epigenetic markers at two key floral integrators,FLOWERING LOCUS T(FT)and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1(SOC1),thereby regulating their expression to trigger the flowering process.We show that HAC1 physically interacts with CONSTANS(CO)in vivo and in vitro.Chromatin immunoprecipitation results indicate that HAC1 directly binds to the FT and SOC1 loci.Loss of HAC1 impairs CO-mediated transcriptional activation of FT and SOC1 in promoting flowering.Moreover,CO mutation leads to the decreased enrichment of HAC1 at FT and SOC1,indicating that CO recruits HAC1 to FT and SOC1.Finally,HAC1,as well as CO,is required for the elevated histone acetylation level at FT and SOC1.Taken together,our finding reveals that HAC1-mediated histone acetylation boots flowering via a CO-dependent activation of FT and SOC1.展开更多
BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational mo...BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational modification,its role in cholelithiasis remains unexplored.AIM To investigate the functional role of succinylation in cholelithiasis and determine its underlying molecular mechanisms.METHODS A murine cholelithiasis model was established through high-fat diet feeding,followed by isolation of mouse gallbladder mucosal epithelial cells(GMECs)for in vitro analysis.Gallbladder tissues and serum samples were collected for subsequent analysis.Inflammatory cytokine production was quantified using enzyme-linked immunosorbent assay.Pyroptosis was analyzed by flow cytometry,while succinylation-and pyroptosis-related protein expression was detected via western blot.RESULTS Our findings demonstrated that lysine acetyltransferase 2A(KAT2A)-mediated succinylation regulated gallstone formation.KAT2A overexpression inhibited the pyroptosis,inflammatory responses,and promoted the activation of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)sig-naling pathway in GMECs.Mechanistically,AMPK exhibited succinylation at lysine 170(K170).Notably,AMPK inhibition significantly increased pyroptosis rates,inflammatory responses,and pyroptosis-related protein ex-pression in GMECs.Furthermore,in vivo experiments revealed that KAT2A overexpression suppressed both inflammation and gallstone formation.CONCLUSION KAT2A-mediated succinylation of AMPK inhibited cholelithiasis progression by modulating the AMPK/SIRT1 signaling pathway,offering potential therapeutic strategies for this condition.展开更多
MicroRNAs （miRNA） that guide sequence-specific posttranscriptional gene silencing play an important role in gene expression required for both developmental processes and responses to environmental conditions in plan...MicroRNAs （miRNA） that guide sequence-specific posttranscriptional gene silencing play an important role in gene expression required for both developmental processes and responses to environmental conditions in plants. However, little is known about the transcriptional and posttranscriptional regulation of miRNA expression. Histone acetylation plays an important role in chromatin remodeling and is required for gene activation. By analyzing the accumulation of subset of miRNAs and the corresponding primary miRNAs in mutants of Arabidopsis, we show that histone acetyltransferase GCN5 （General control non-repressed protein 5） has a general repressive effect on miRNA production, while it is required for the expression of a subset of （e.g. stress-inducible） MIRNA genes. The general negative function of GCN5 in miRNA production is likely achieved through an indirect repression of the miRNA machinery genes such as DICER LIKE1 （DCL1）, SERRATE （SE）, HYPONASTIC LEAVES1 （HYL1） and ARGONAUTE1 （AGO1）. Chromatin immunoprecipitation assays revealed that GCN5 targets to a subset of MIRNA genes and is required for acetylation of histone H3 lysine 14 at these loci. Moreover, inhibition of histone deacetylation by trichostatin A treatment or in histone deacetylase gene mutants impaired the accumulation of certain miRNAs. These data together suggest that Arabidopsis GCN5 interferes with the miRNA pathway at both the transcriptional and posttranscriptional levels and histone acetylation/deacetylation is an epigenetic mechanism involved in the regulation of miRNA production.展开更多
We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfred...We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfredii Hance, as compared with its non-hyperaccumulating ecotype (NHE). The results show that plant growth was inhibited in NHE but promoted in HE when exposed to high Cd level. Cd concentrations in leaves and shoots rapidly increased in HE rather than in NHE, and they became much higher in HE than in NHE along with increasing treatment time and Cd supply levels. ATPS activity was higher in HE than in NHE in all Cd treatments, and increased with increasing Cd supply levels in both HE and NHE when exposed to Cd treatment within 8 h. However, a marked difference of ATPS activity between HE and NHE was found with Cd treatment for 168 h, where ATPS activity increased in HE but decreased in NHE. Similarly, SAT activity was higher in HE than in NHE at all Cd treatments, but was more sensitive in NHE than in HE. Both ATPS and SAT activities in NHE leaves tended to decrease with increasing treatment time after 8 h at all Cd levels. The results reveal the different responses in sulfur assimilation enzymes and Cd accumulation between HE and NHE. With increasing Cd stress, the activities of sulfur assimilation enzymes (ATPS and SAT) were induced in HE, which may contribute to Cd accumulation in the hyperaccumulator Sedum alfredii Hance.展开更多
BACKGROUND： The main components of the traditional Chinese medicine compound Nao Yikang have been shown to possibly alleviate neural damage. OBJECTIVE： To observe the effects of Nao Yikang on expression of choline a...BACKGROUND： The main components of the traditional Chinese medicine compound Nao Yikang have been shown to possibly alleviate neural damage. OBJECTIVE： To observe the effects of Nao Yikang on expression of choline acetyltransferase （CHAT） and caspase-3 in the rat brains of an experimental Alzheimer＇s disease （AD） model, and to investigate the mechanisms of potential neuroprotective effects. DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Department of Pathophysiology, Medical School of Nantong University between November 2006 and December 2007. MATERIALS： The main active components of Nao Yikang were as follows： prepared polygonum multiflorum, Rhizoma anemarrhenae, and Rhizoma acori tatarinowii. Nao Yikang granules were prepared by Nantong Hospital of Traditional Chinese Medicine. Ibotenic acid （IBO） was purchased from Sigma-Aldrich, USA, ChAT goat anti-rat antibody from Chemicon, USA, and cleaved caspase-3 rabbit anti-rat （Asp175） （5A1） antibody from Cell Signaling, USA. METHODS： A total of 60 male, Sprague Dawley rats （2 months old） were randomly assigned to 6 groups： sham-surgery, model, Nao Yikang 1.73, 3.45, 6.90 g/kg per day, and piracetam, with 10 rats in each group. Bilateral infusions of 5 pg IBO into the nucleus basalis of Meynert were performed with Hamilton syringe and stereotaxic apparatus for AD model establishment. For the sham-surgery group, rats received 1 μL saline in the identical stereotaxic position. From the second day, Nao Yikang groups were administrated 1.73, 3.45, and 6.90 g/kg per day Nao Yikang, respectively, while the piracetam group received 0.04 g/mL piracetam, the model group received 0.5% sodium carboxymethyl cellulose, and the sham-surgery group received normal saline. Rats were intragastrically administered 1 mL/100 g daily for 28 consecutive days. MAIN OUTCOME MEASURES： Following treatment of the various solutions for 28 days, Western blot was utilized to observe ChAT expression in the frontal cortex of AD rats, and immunohistochemistry was applied to quantify caspase-3-positive cells in the frontal cortex. RESULTS： ChAT protein expression significantly decreased in the model group （P 〈 0.01）, however caspase-3 expression was significantly elevated （P 〈 0.01） compared with the sham-surgery group. Compared with the model group, ChAT protein expression increased in the Nao Yikang 1.73 g/kg per day, 3.45 g/kg per day, 6.90 g/kg per day groups, and the piracetam group （P 〈 0.05 or P 〈 0.01） and the number of caspase-3-positive cells decreased in the Nao Yikang 3.45 g/kg per day and 6.90 g/kg per day groups （P 〈 0.01）. However, there was no change in the number of caspase-3-positive cells in the 3.45 g/kg per day group. CONCLUSION： The traditional Chinese medicine compound Nao Yikang increased ChAT protein expression and suppressed caspase-3 expression in the frontal cortex in a dose-dependent manner.展开更多
Histone acetylation is indispensable in the process of crops resisting abiotic stress,which is jointly catalyzed by histone acetyltransferases and deacetylases.However,the mechanism of regulating salt tolerance throug...Histone acetylation is indispensable in the process of crops resisting abiotic stress,which is jointly catalyzed by histone acetyltransferases and deacetylases.However,the mechanism of regulating salt tolerance through histone acetyltransferase GCN5 is still unclear.We revealed that GCN5 can catalyze the acetylation of canonical H3 and H4 lysine residues both in vivo and in vitro in rice.The knockout mutants and RNA interference lines of Os GCN5 exhibited severe growth inhibition and defects in salt tolerance,while the over-expression of Os GCN5 enhanced the salt tolerance of rice seedlings,indicating that Os GCN5 positively regulated the response of rice to salt stress.RNA-seq analysis suggested Os GCN5 may positively regulate the salt tolerance of rice by inhibiting the expression of Os HKT2;1 or other salt-responsive genes.Taken together,our study indicated that GCN5 plays a key role in enhancing salt tolerance in rice.展开更多
We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and...We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and 21 days. The results revealed that estrogen improved microvasculature in the hippocampus of chronic cerebral ischemic rats, upregulated Bcl-2 protein expression, downregulated Bax protein expression, increased choline acetyltransferase expression in hippocampal cholinergic neurons, and suppressed hippocampal neuronal apoptosis. These findings indicate that estrogen can protect hippocampal neurons in rats with chronic cerebral ischemia.展开更多
BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji(SPXJ)herbal decoction formula is effective in suppressing hepatocellular carcinoma(HCC),but the underlying mechanisms are not known.Therefore,this study i...BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji(SPXJ)herbal decoction formula is effective in suppressing hepatocellular carcinoma(HCC),but the underlying mechanisms are not known.Therefore,this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1(ACAT1)-regulated cellular stiffness.Through a series of experiments,we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1,lowering the level of cholesterol in the cell membrane,and altering the cellular stiffness,which provides a new idea for the research of traditional Chinese medicine against HCC.AIM To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC.METHODS HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice.The apoptotic rate and proliferative,invasive,and migratory abilities of control and SPXJ-treated HCC cells were compared.Atomic force microscopy was used to determine the cell surface morphology and the Young’s modulus values of the control and SPXJ-treated HCC cells.Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit.ACAT1 protein levels were estimated using western blotting.RESULTS Compared with the vehicle group,SPXJ serum considerably reduced proliferation of HCC cells,increased stiffness and apoptosis of HCC cells,inhibited migration and invasion of HCC cells,decreased plasma membrane cholesterol levels,and upregulated ACAT1 protein levels.However,treatment of HCC cells with the water-soluble cholesterol promoted proliferation,migration,and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels,but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control.CONCLUSION SPXJ formula inhibited proliferation,invasion,and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression.展开更多
BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary...BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE： To explore morphological changes of choline acetyltransferase （ChAT）-positive neurons in the paraolivary nucleus （PON） of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING： Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS： A total of 48 healthy guinea pigs were randomly divided into model （n = 40） and control （n = 8） groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS： Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES： Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS： ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration （P 〈 0.05）. In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection （P 〈 0.05）, whereas cell number significantly decreased at ;three weeks after injection （P 〈 0.05）. Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration （P 〈 0.05）. CONCLUSION： Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.展开更多
BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,tr...BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,treatment is only rehabilitation and surgery for cleft lip and palate.CASE SUMMARY The proband was a 2-years-8-months-old girl.Familial history was negative for congenital malformations or intellectual disability.The patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and palate.Brain magnetic resonance imaging showed cortical atrophy and band heterotopia.Her motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were detected.CONCLUSION There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 deletion.We describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular defect.Additional clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.展开更多
A diffusion-reaction, two-compartment model was used to explore the bifurcation and chaotic behavior of acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT) coupled enzymes system. The effects of hydrogen i...A diffusion-reaction, two-compartment model was used to explore the bifurcation and chaotic behavior of acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT) coupled enzymes system. The effects of hydrogen ion feed concentrations, choline (Ch) and acetylcholine (ACh) feed concentrations, as bifurcation parameters on the system performance are studied. It is found that hydrogen ions play an important role in creating potential differences through the plasma membranes. Detailed bifurcation analysis over a wide range of parameters is carried out in order to uncover some of the qualitative changes of the system such as hysteresis, multiplicity, Hopf bifurcation, boundary crises bifurcation, periodic transient, and other complex dynamics. Some of the obtained results relate to the phenomena occurring in the physiological experiments like periodic stimulation of neural cells and irregular functioning of acetylcholine receptors. The model depends on real kinetics expressions and parameters obtained from the literature, so the results can be used to direct more systematic research on cholinergic disorder.展开更多
Background: Esophageal cancer is one of the primary death causes leading by cancer in the world, which is high morbidity and mortality. Epigenetic acetylation modification participates in and regulates the prolif...Background: Esophageal cancer is one of the primary death causes leading by cancer in the world, which is high morbidity and mortality. Epigenetic acetylation modification participates in and regulates the proliferation, invasion, and metastasis of various tumor cells, and the acetylation modification of tumor proteins involved by acetyltransferases may be one of the important mechanisms of esophageal carcinogenesis. The aim of this study was to investigate the correlation of acetyltransferase P300 and Survivin acetylation in esophageal cancer pathogenesis and its molecular mechanism. Methods: Fifty-five cases of esophageal cancer tissues and adjacent cancer tissues were collected, Survivin and P300 protein expression was measured by immunohistochemistry (SP) and protein blotting (Western Blot);Survivin acetylated protein levels were measured by coimmunoprecipitation (Co-IP);bioinformatics predicted the relationship between P300 and Survivin as the substrate, and fluorescence immunohistochemistry (IF) to verify the localization and expression of Survivin and P300 in esophageal cancer tissues;the correlation of Survivin acetylation, P300 and clinical cases characteristics was analyzed by statistics. P300 siRNA sequences were structured and transfected into EC109 cells. P300 protein expression and Survivin acetylated protein levels were determined by Co-IP. Cell viability was determined by the MTT assay, Scratch healing and Transwell chamber assay examined cell migration and invasion ability. Results: Survivin and P300 protein expression was significantly increased in human esophageal cancer tissues and EC109 cells. The Survivin protein was acetylated in esophageal cancer tissues and EC109 cells, and its protein acetylation rate was significantly increased;bioinformatics predicted that the acetyltransferase P300 could catalyze the acetylation of Survivin as a substrate, and the fluorescence immunohistochemistry confirmed that both Survivin and P300 simultaneously showed a high expression state in cancer tissues;Survivin acetylation and P300 expression;Survivin acetylation and P300 were closely related with esophageal cancer stage, tissue differentiation and lymph node metastasis. The vitro experiments showed that P300 RNA interference in esophageal cancer cells can significantly reduce the Survivin protein acetylation level, while inhibiting the survival, migration and invasion capacity of EC109 cells. Conclusion: P300 has a correlation with Survivin acetylation in the lespathological process of esophageal cancer, P300 may be an important upstream molecule of Survivin acetylation and has an important potential value in the diagnosis and treatment of esophageal cancer.展开更多
Tumor metabolism often interferes with the immune microenvironment.Although natural killer(NK)cells play pivotal roles in antitumor immunity,the connection between NK cells and tumor metabolism remains unclear.Our sys...Tumor metabolism often interferes with the immune microenvironment.Although natural killer(NK)cells play pivotal roles in antitumor immunity,the connection between NK cells and tumor metabolism remains unclear.Our systematic analysis of multiomics data and survival data from colorectal cancer(CRC)patients uncovered a novel association between mitochondrial acetyl-CoA acetyltransferase 1(ACAT1)and NK cell infiltration that influences disease progression.ACAT1,a metabolic enzyme involved in reversible conversion of acetoacetyl-CoA to two molecules of acetyl-CoA,exhibits nuclear protein acetylation activity through its translocation.Under immune stimulation,mitochondrial ACAT1 can be phosphorylated at serine 60(S60)and enters the nucleus;however,this process is hindered in nutrient-poor tumor microenvironments.Nuclear ACAT1 directly acetylates lysine 146 of p50(NFKB1),attenuating its DNA binding and transcriptional repression activity and thereby increasing the expression of immune-related factors,which in turn promotes NK cell recruitment and activation to suppress colorectal cancer growth.Furthermore,significant associations are found among low nuclear ACAT1 levels,decreased S60 phosphorylation,and reduced NK cell infiltration,as well as poor prognosis in CRC.Our findings reveal an unexpected function of ACAT1 as a nuclear acetyltransferase and elucidate its role in NK cell-dependent antitumor immunity through p50 acetylation.展开更多
S.Lehrer and P.H.Rheinstein,“Alignment of Human KAT2A(GCN5)Histone Acetyltransferase and SARS-CoV-2 Orf8 Viral Proteins,”Chronic Diseases and Translational Medicine 9(2023):263–265.https://doi.org/10.1002/cdt3.56.T...S.Lehrer and P.H.Rheinstein,“Alignment of Human KAT2A(GCN5)Histone Acetyltransferase and SARS-CoV-2 Orf8 Viral Proteins,”Chronic Diseases and Translational Medicine 9(2023):263–265.https://doi.org/10.1002/cdt3.56.The original article included a Conflict of Interest statement which stated:“The authors declare no conflicts of interest.”The journal and the publisher have determined that a conflict of interest on behalf of each author was not declared at publication.The journal and the publisher have had sufficient communication with the authors via email after raising questions about the Conflict of Interest in the article.The authors declared that there was no undeclared Conflict of Interest and further stated that their individual affiliations with commercial entities did not influence the research findings.展开更多
Although two Enhancer of Polycomb-like proteins,EPL1 A and EPL1 B(EPL1 A/B),are known to be conserved and characteristic subunits of the Nu A4-type histone acetyltransferase complex in Arabidopsis thaliana,the biologi...Although two Enhancer of Polycomb-like proteins,EPL1 A and EPL1 B(EPL1 A/B),are known to be conserved and characteristic subunits of the Nu A4-type histone acetyltransferase complex in Arabidopsis thaliana,the biological function of EPL1 A/B and the mechanism by which EPL1 A/B function in the complex remain unknown.Here,we report that EPL1 A/B are required for the histone acetyltransferase activity of the Nu A4 complex on the nucleosomal histone H4 in vitro and for the enrichment of histone H4 K5 acetylation at thousands of protein-coding genes in vivo.Our results suggest that EPL1 A/B are required for linking the Nu A4 catalytic subunits HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY 1(HAM1)and HAM2 with accessory subunits in the Nu A4 complex.EPL1 A/B function redundantly in regulating plant development especially in chlorophyll biosynthesis and de-etiolation.The EPL1 A/B-dependent transcription and H4 K5 Ac are enriched at genes involved in chlorophyll biosynthesis and photosynthesis.We also find that EAF6,another characteristic subunit of the Nu A4 complex,contributes to de-etiolation.These results suggest that the Arabidopsis Nu A4 complex components function as a whole to mediate histone acetylation and transcriptional activation specifically at light-responsive genes and are critical for photomorphogenesis.展开更多
The mammalian MOF （male absent on the first）, a member of the MYST （MOZ, YBF2, SAS2, and Tip60） family of histone acetyltransferases （HATs）, is the major enzyme that catalyzes the acetylation of histone H4 on ly...The mammalian MOF （male absent on the first）, a member of the MYST （MOZ, YBF2, SAS2, and Tip60） family of histone acetyltransferases （HATs）, is the major enzyme that catalyzes the acetylation of histone H4 on lysine 16. Acetylation of K16 is a prevalent mark associated with chromatin decondensation. MOF has recently been shown to play an essential role in maintaining normal cell functions. In this study, we discuss the important roles of MOF in DNA damage repair, apoptosis, and tumorigenesis. We also analyze the role of MOF as a key regulator of the core transcriptional network of embryonic stem cells.展开更多
Histone acetyltransferase(HAT)catalyzes histone acetylation and is involved in plant growth and development and stress responses.Here,37 CitHAT genes were identifed in Citrus clementina.Their physicochemical propertie...Histone acetyltransferase(HAT)catalyzes histone acetylation and is involved in plant growth and development and stress responses.Here,37 CitHAT genes were identifed in Citrus clementina.Their physicochemical properties,chromosomal location,gene structure,conserved domain and motif,and cis-acting elements were characterized.CitHATs were classifed into four subfamilies based on protein sequence homology,which was strongly supported by gene structure,conserved domain,and motif analysis.The cis-acting elements in gene promoter regions were predicted to be associated with the regulation of plant growth,stress resistance,and response to hormones.Phenotypic and transcriptomic analyses of citrus callus with mock treatment and HAT inhibitor treatment revealed that increased citric acid content in inhibitor treatment may be attributed to differential expression of CitPEPCK2 and CitGS2,which may be due to the hypo-acetylation of histone H3.The expression patterns of CitHATs in citrus fruit development stages showed that CitHAG11 and CitHAG28 exhibited a negative correlation with citric acid content.Our study associates the potential function of histone acetyltransferases in citrate metabolism and extends the molecular mechanism of citrate metabolism in fruits.展开更多
When exposing to environmental stress or internal damage, such as genotoxic stress, oxidative stress, and heat stress, cells produce a series of adaptive responses called cellular stress responses. The major proteins ...When exposing to environmental stress or internal damage, such as genotoxic stress, oxidative stress, and heat stress, cells produce a series of adaptive responses called cellular stress responses. The major proteins involved in cellular stress are heat shock proteins （HSPs）.展开更多
Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play ...Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.展开更多
基金supported by the National Natural Science Foundation of China to Z.L.(32300474)and to C.L.(32470346 and 32270362)the Guangdong Basic and Applied Basic Research Foundation to C.L.(2024A1515010612)the Fundamental Research Funds for the Central Universities to X.S.(24qnpy078).
文摘Chromatin modifications,including histone acetylation,play essential roles in regulating flowering.The CBP/p300 family HISTONE ACETYLTRANSFERASE 1(HAC1),which mediates histone acetylation,promotes the process of floral transition;however,the precise mechanism remains largely unclear.Specifically,how HAC1 is involved in the flowering regulatory network and which genes are the direct targets of HAC1 during flowering regulation are still unknown.In this study,we elucidate the critical function of HAC1 in promoting flowering via exerting active epigenetic markers at two key floral integrators,FLOWERING LOCUS T(FT)and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1(SOC1),thereby regulating their expression to trigger the flowering process.We show that HAC1 physically interacts with CONSTANS(CO)in vivo and in vitro.Chromatin immunoprecipitation results indicate that HAC1 directly binds to the FT and SOC1 loci.Loss of HAC1 impairs CO-mediated transcriptional activation of FT and SOC1 in promoting flowering.Moreover,CO mutation leads to the decreased enrichment of HAC1 at FT and SOC1,indicating that CO recruits HAC1 to FT and SOC1.Finally,HAC1,as well as CO,is required for the elevated histone acetylation level at FT and SOC1.Taken together,our finding reveals that HAC1-mediated histone acetylation boots flowering via a CO-dependent activation of FT and SOC1.
基金Supported by National Natural Science Foundation of China,No.82000579 and No.81870205Natural Science Foundation of Shandong Province,No.ZR2021QH061 and No.ZR2021QH186.
文摘BACKGROUND Cholelithiasis is a prevalent biliary tract disorder primarily characterized by gallbladder or biliary stone formation.Although succinylation has been exten-sively studied as a protein post-translational modification,its role in cholelithiasis remains unexplored.AIM To investigate the functional role of succinylation in cholelithiasis and determine its underlying molecular mechanisms.METHODS A murine cholelithiasis model was established through high-fat diet feeding,followed by isolation of mouse gallbladder mucosal epithelial cells(GMECs)for in vitro analysis.Gallbladder tissues and serum samples were collected for subsequent analysis.Inflammatory cytokine production was quantified using enzyme-linked immunosorbent assay.Pyroptosis was analyzed by flow cytometry,while succinylation-and pyroptosis-related protein expression was detected via western blot.RESULTS Our findings demonstrated that lysine acetyltransferase 2A(KAT2A)-mediated succinylation regulated gallstone formation.KAT2A overexpression inhibited the pyroptosis,inflammatory responses,and promoted the activation of the adenosine monophosphate-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)sig-naling pathway in GMECs.Mechanistically,AMPK exhibited succinylation at lysine 170(K170).Notably,AMPK inhibition significantly increased pyroptosis rates,inflammatory responses,and pyroptosis-related protein ex-pression in GMECs.Furthermore,in vivo experiments revealed that KAT2A overexpression suppressed both inflammation and gallstone formation.CONCLUSION KAT2A-mediated succinylation of AMPK inhibited cholelithiasis progression by modulating the AMPK/SIRT1 signaling pathway,offering potential therapeutic strategies for this condition.
文摘MicroRNAs （miRNA） that guide sequence-specific posttranscriptional gene silencing play an important role in gene expression required for both developmental processes and responses to environmental conditions in plants. However, little is known about the transcriptional and posttranscriptional regulation of miRNA expression. Histone acetylation plays an important role in chromatin remodeling and is required for gene activation. By analyzing the accumulation of subset of miRNAs and the corresponding primary miRNAs in mutants of Arabidopsis, we show that histone acetyltransferase GCN5 （General control non-repressed protein 5） has a general repressive effect on miRNA production, while it is required for the expression of a subset of （e.g. stress-inducible） MIRNA genes. The general negative function of GCN5 in miRNA production is likely achieved through an indirect repression of the miRNA machinery genes such as DICER LIKE1 （DCL1）, SERRATE （SE）, HYPONASTIC LEAVES1 （HYL1） and ARGONAUTE1 （AGO1）. Chromatin immunoprecipitation assays revealed that GCN5 targets to a subset of MIRNA genes and is required for acetylation of histone H3 lysine 14 at these loci. Moreover, inhibition of histone deacetylation by trichostatin A treatment or in histone deacetylase gene mutants impaired the accumulation of certain miRNAs. These data together suggest that Arabidopsis GCN5 interferes with the miRNA pathway at both the transcriptional and posttranscriptional levels and histone acetylation/deacetylation is an epigenetic mechanism involved in the regulation of miRNA production.
基金supported by the National Natural Science Foundation of China (No. 30630046)the Hi-Tech Research and Development Program (863) of China (No. 2006AA06Z386)the Program for Changjiang Scholars and Innovative Research Team in University, China (No. IRT0536)
文摘We studied the responses of the activities of adenosine-triphosphate (ATP) sulfurylase (ATPS) and serine acetyltransferase (SAT) to cadmium (Cd) levels and treatment time in hyperaccumulating ecotype (HE) Sedum alfredii Hance, as compared with its non-hyperaccumulating ecotype (NHE). The results show that plant growth was inhibited in NHE but promoted in HE when exposed to high Cd level. Cd concentrations in leaves and shoots rapidly increased in HE rather than in NHE, and they became much higher in HE than in NHE along with increasing treatment time and Cd supply levels. ATPS activity was higher in HE than in NHE in all Cd treatments, and increased with increasing Cd supply levels in both HE and NHE when exposed to Cd treatment within 8 h. However, a marked difference of ATPS activity between HE and NHE was found with Cd treatment for 168 h, where ATPS activity increased in HE but decreased in NHE. Similarly, SAT activity was higher in HE than in NHE at all Cd treatments, but was more sensitive in NHE than in HE. Both ATPS and SAT activities in NHE leaves tended to decrease with increasing treatment time after 8 h at all Cd levels. The results reveal the different responses in sulfur assimilation enzymes and Cd accumulation between HE and NHE. With increasing Cd stress, the activities of sulfur assimilation enzymes (ATPS and SAT) were induced in HE, which may contribute to Cd accumulation in the hyperaccumulator Sedum alfredii Hance.
基金Supported by: the Natural Science Foundation of Jiangsu Province, No. BK2004048Social Development and Technology Plan of Nantong City, No. K2008009
文摘BACKGROUND： The main components of the traditional Chinese medicine compound Nao Yikang have been shown to possibly alleviate neural damage. OBJECTIVE： To observe the effects of Nao Yikang on expression of choline acetyltransferase （CHAT） and caspase-3 in the rat brains of an experimental Alzheimer＇s disease （AD） model, and to investigate the mechanisms of potential neuroprotective effects. DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Department of Pathophysiology, Medical School of Nantong University between November 2006 and December 2007. MATERIALS： The main active components of Nao Yikang were as follows： prepared polygonum multiflorum, Rhizoma anemarrhenae, and Rhizoma acori tatarinowii. Nao Yikang granules were prepared by Nantong Hospital of Traditional Chinese Medicine. Ibotenic acid （IBO） was purchased from Sigma-Aldrich, USA, ChAT goat anti-rat antibody from Chemicon, USA, and cleaved caspase-3 rabbit anti-rat （Asp175） （5A1） antibody from Cell Signaling, USA. METHODS： A total of 60 male, Sprague Dawley rats （2 months old） were randomly assigned to 6 groups： sham-surgery, model, Nao Yikang 1.73, 3.45, 6.90 g/kg per day, and piracetam, with 10 rats in each group. Bilateral infusions of 5 pg IBO into the nucleus basalis of Meynert were performed with Hamilton syringe and stereotaxic apparatus for AD model establishment. For the sham-surgery group, rats received 1 μL saline in the identical stereotaxic position. From the second day, Nao Yikang groups were administrated 1.73, 3.45, and 6.90 g/kg per day Nao Yikang, respectively, while the piracetam group received 0.04 g/mL piracetam, the model group received 0.5% sodium carboxymethyl cellulose, and the sham-surgery group received normal saline. Rats were intragastrically administered 1 mL/100 g daily for 28 consecutive days. MAIN OUTCOME MEASURES： Following treatment of the various solutions for 28 days, Western blot was utilized to observe ChAT expression in the frontal cortex of AD rats, and immunohistochemistry was applied to quantify caspase-3-positive cells in the frontal cortex. RESULTS： ChAT protein expression significantly decreased in the model group （P 〈 0.01）, however caspase-3 expression was significantly elevated （P 〈 0.01） compared with the sham-surgery group. Compared with the model group, ChAT protein expression increased in the Nao Yikang 1.73 g/kg per day, 3.45 g/kg per day, 6.90 g/kg per day groups, and the piracetam group （P 〈 0.05 or P 〈 0.01） and the number of caspase-3-positive cells decreased in the Nao Yikang 3.45 g/kg per day and 6.90 g/kg per day groups （P 〈 0.01）. However, there was no change in the number of caspase-3-positive cells in the 3.45 g/kg per day group. CONCLUSION： The traditional Chinese medicine compound Nao Yikang increased ChAT protein expression and suppressed caspase-3 expression in the frontal cortex in a dose-dependent manner.
基金supported by the Key R&D Program of Jiangsu Province (Grant No.BE2022335)the Jiangsu Province Government (Grant No.JBGS[2021]001)+3 种基金the Natural Science Foundation of Jiangsu Province (Grant No.BK20230295)the Project of Zhongshan Biological Breeding Laboratory (Grant No.BM2022008-02)the Outstanding Youth Fund of Jiangsu Province (Grant No.BK20230013)the Priority Academic Program Development of Jiangsu Higher Education Institutions in China。
文摘Histone acetylation is indispensable in the process of crops resisting abiotic stress,which is jointly catalyzed by histone acetyltransferases and deacetylases.However,the mechanism of regulating salt tolerance through histone acetyltransferase GCN5 is still unclear.We revealed that GCN5 can catalyze the acetylation of canonical H3 and H4 lysine residues both in vivo and in vitro in rice.The knockout mutants and RNA interference lines of Os GCN5 exhibited severe growth inhibition and defects in salt tolerance,while the over-expression of Os GCN5 enhanced the salt tolerance of rice seedlings,indicating that Os GCN5 positively regulated the response of rice to salt stress.RNA-seq analysis suggested Os GCN5 may positively regulate the salt tolerance of rice by inhibiting the expression of Os HKT2;1 or other salt-responsive genes.Taken together,our study indicated that GCN5 plays a key role in enhancing salt tolerance in rice.
基金a grant by Hebei Provincial Education Ministry,No.Z200632
文摘We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and 21 days. The results revealed that estrogen improved microvasculature in the hippocampus of chronic cerebral ischemic rats, upregulated Bcl-2 protein expression, downregulated Bax protein expression, increased choline acetyltransferase expression in hippocampal cholinergic neurons, and suppressed hippocampal neuronal apoptosis. These findings indicate that estrogen can protect hippocampal neurons in rats with chronic cerebral ischemia.
基金Supported by the National Natural Science Foundation of China,No.82074425Hunan Science and Technology Planning Project,No.2016SK2051 and No.2023SK2057the Hunan Provincial Administration of Traditional Chinese Medicine Research Project,No.B2023089.
文摘BACKGROUND Previous studies have shown that the Shi-pi-xiao-ji(SPXJ)herbal decoction formula is effective in suppressing hepatocellular carcinoma(HCC),but the underlying mechanisms are not known.Therefore,this study investigated whether the antitumor effects of the SPXJ formula in treating HCC were mediated by acetyl-coA acetyltransferase 1(ACAT1)-regulated cellular stiffness.Through a series of experiments,we concluded that SPXJ inhibits the progression of HCC by upregulating the expression level of ACAT1,lowering the level of cholesterol in the cell membrane,and altering the cellular stiffness,which provides a new idea for the research of traditional Chinese medicine against HCC.AIM To investigate the anti-tumor effects of the SPXJ formula on the malignant progression of HCC.METHODS HCC cells were cultured in vitro with SPXJ-containing serum prepared by injecting SPXJ formula into wild-type mice.The apoptotic rate and proliferative,invasive,and migratory abilities of control and SPXJ-treated HCC cells were compared.Atomic force microscopy was used to determine the cell surface morphology and the Young’s modulus values of the control and SPXJ-treated HCC cells.Plasma membrane cholesterol levels in HCC cells were detected using the Amplex Red cholesterol detection kit.ACAT1 protein levels were estimated using western blotting.RESULTS Compared with the vehicle group,SPXJ serum considerably reduced proliferation of HCC cells,increased stiffness and apoptosis of HCC cells,inhibited migration and invasion of HCC cells,decreased plasma membrane cholesterol levels,and upregulated ACAT1 protein levels.However,treatment of HCC cells with the water-soluble cholesterol promoted proliferation,migration,and invasion of HCC cells as well as decreased cell stiffness and plasma membrane cholesterol levels,but did not alter the apoptotic rate and ACAT1 protein expression levels compared with the vehicle control.CONCLUSION SPXJ formula inhibited proliferation,invasion,and migration of HCC cells by decreasing plasma membrane cholesterol levels and altering cellular stiffness through upregulation of ACAT1 protein expression.
文摘BACKGROUND： It is generally accepted that gentamicin can damage the cochlear nerve and acoustic nerve. In recent years, scholars have focused on neuronal changes and neurochemical information in the brainstem primary auditory center. OBJECTIVE： To explore morphological changes of choline acetyltransferase （ChAT）-positive neurons in the paraolivary nucleus （PON） of guinea pigs, and the effect on hearing following gentamicin injection. DESIGN, TIME AND SETTING： Randomized grouping and morphological observational study was performed at Animal Experimental Center of General Hospital of Shenyang Military Area Command of Chinese PLA from January to August 2007. MATERIALS： A total of 48 healthy guinea pigs were randomly divided into model （n = 40） and control （n = 8） groups. The model group was divided into five subgroups at five time points of 1 and 3 days, 1, 2, and 3 weeks. METHODS： Guinea pigs in the model group were intraperitoneally injected with gentamicin, and those in the control group were intraperitoneally injected with the same volume of saline. MAIN OUTCOME MEASURES： Auditory brainstem-evoked potential was used to record auditory threshold; distribution and morphological changes of ChAT-positive neurons in the PON were observed with immunohistochemistry; section area and gray value of ChAT-positive neurons were measured with Quantimet 570 image-analyzing system. RESULTS： ChAT-positive neurons were diffusedly distributed in the PON. The majority was composed of large, round cells, with positive neurites that could be clearly observed. Following gentamicin injection, the positive neurons displayed an irregular outline, and their neurites began to shorten and disappear. The gray value increased with prolonged gentamicin administration （P 〈 0.05）. In addition, the somatic cross-sectional area was enlarged in the model group at 1 and 3 days after injection （P 〈 0.05）, whereas cell number significantly decreased at ;three weeks after injection （P 〈 0.05）. Starting at 3-4 days, behavioral features and auditory degrees became gradually aggravated with prolonged gentamicin administration （P 〈 0.05）. CONCLUSION： Gentamicin damaged ChAT-positive neurons in the PON, and long-term gentamicin treatment aggravated hearing impairment.
基金Supported by PAEP,2018 and PAPIIT IN219419,DGAPA,Universidad Nacional Autónoma de México,No.IN219419.
文摘BACKGROUND We described the main features of an infant diagnosed with facial dysmorphic,language failure,intellectual disability and congenital malformations to strengthen our understanding of the disease.Currently,treatment is only rehabilitation and surgery for cleft lip and palate.CASE SUMMARY The proband was a 2-years-8-months-old girl.Familial history was negative for congenital malformations or intellectual disability.The patient had microcephaly,upward-slanting palpebral fissures,depressed nasal bridge,bulbous nose and bilateral cleft lip and palate.Brain magnetic resonance imaging showed cortical atrophy and band heterotopia.Her motor and intellectual development is delayed.A submicroscopic deletion in 11p13 involving the elongator acetyltransferase complex subunit 4 gene(ELP4)and a loss of heterozygosity in Xq25-q26.3 were detected.CONCLUSION There is no treatment for the ELP4 deletion caused by a submicroscopic 11p3 deletion.We describe a second case of deletion of the ELP4 gene without aniridia,which confirms the association between ELP4 gene with several defects and absence of this ocular defect.Additional clinical data in the deletion of the ELP4 gene as cleft palate,facial dysmorphism,and changes at level brain could be associated to this gene or be part of the effect of the recessives genes involved in the loss of heterozygosity region of Xq25-26.3.
文摘A diffusion-reaction, two-compartment model was used to explore the bifurcation and chaotic behavior of acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT) coupled enzymes system. The effects of hydrogen ion feed concentrations, choline (Ch) and acetylcholine (ACh) feed concentrations, as bifurcation parameters on the system performance are studied. It is found that hydrogen ions play an important role in creating potential differences through the plasma membranes. Detailed bifurcation analysis over a wide range of parameters is carried out in order to uncover some of the qualitative changes of the system such as hysteresis, multiplicity, Hopf bifurcation, boundary crises bifurcation, periodic transient, and other complex dynamics. Some of the obtained results relate to the phenomena occurring in the physiological experiments like periodic stimulation of neural cells and irregular functioning of acetylcholine receptors. The model depends on real kinetics expressions and parameters obtained from the literature, so the results can be used to direct more systematic research on cholinergic disorder.
文摘Background: Esophageal cancer is one of the primary death causes leading by cancer in the world, which is high morbidity and mortality. Epigenetic acetylation modification participates in and regulates the proliferation, invasion, and metastasis of various tumor cells, and the acetylation modification of tumor proteins involved by acetyltransferases may be one of the important mechanisms of esophageal carcinogenesis. The aim of this study was to investigate the correlation of acetyltransferase P300 and Survivin acetylation in esophageal cancer pathogenesis and its molecular mechanism. Methods: Fifty-five cases of esophageal cancer tissues and adjacent cancer tissues were collected, Survivin and P300 protein expression was measured by immunohistochemistry (SP) and protein blotting (Western Blot);Survivin acetylated protein levels were measured by coimmunoprecipitation (Co-IP);bioinformatics predicted the relationship between P300 and Survivin as the substrate, and fluorescence immunohistochemistry (IF) to verify the localization and expression of Survivin and P300 in esophageal cancer tissues;the correlation of Survivin acetylation, P300 and clinical cases characteristics was analyzed by statistics. P300 siRNA sequences were structured and transfected into EC109 cells. P300 protein expression and Survivin acetylated protein levels were determined by Co-IP. Cell viability was determined by the MTT assay, Scratch healing and Transwell chamber assay examined cell migration and invasion ability. Results: Survivin and P300 protein expression was significantly increased in human esophageal cancer tissues and EC109 cells. The Survivin protein was acetylated in esophageal cancer tissues and EC109 cells, and its protein acetylation rate was significantly increased;bioinformatics predicted that the acetyltransferase P300 could catalyze the acetylation of Survivin as a substrate, and the fluorescence immunohistochemistry confirmed that both Survivin and P300 simultaneously showed a high expression state in cancer tissues;Survivin acetylation and P300 expression;Survivin acetylation and P300 were closely related with esophageal cancer stage, tissue differentiation and lymph node metastasis. The vitro experiments showed that P300 RNA interference in esophageal cancer cells can significantly reduce the Survivin protein acetylation level, while inhibiting the survival, migration and invasion capacity of EC109 cells. Conclusion: P300 has a correlation with Survivin acetylation in the lespathological process of esophageal cancer, P300 may be an important upstream molecule of Survivin acetylation and has an important potential value in the diagnosis and treatment of esophageal cancer.
基金supported by the National Key R&D Program of China(2023YFC3402100)National Natural Science Foundation of China(82273241,82303224,82372826)+2 种基金Guangdong Basic and Applied Basic Research Foundation(SL2023A04J01630)Sanming Project of Medicine in Shenzhen(SZSM202211017)Cancer Innovative Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004).
文摘Tumor metabolism often interferes with the immune microenvironment.Although natural killer(NK)cells play pivotal roles in antitumor immunity,the connection between NK cells and tumor metabolism remains unclear.Our systematic analysis of multiomics data and survival data from colorectal cancer(CRC)patients uncovered a novel association between mitochondrial acetyl-CoA acetyltransferase 1(ACAT1)and NK cell infiltration that influences disease progression.ACAT1,a metabolic enzyme involved in reversible conversion of acetoacetyl-CoA to two molecules of acetyl-CoA,exhibits nuclear protein acetylation activity through its translocation.Under immune stimulation,mitochondrial ACAT1 can be phosphorylated at serine 60(S60)and enters the nucleus;however,this process is hindered in nutrient-poor tumor microenvironments.Nuclear ACAT1 directly acetylates lysine 146 of p50(NFKB1),attenuating its DNA binding and transcriptional repression activity and thereby increasing the expression of immune-related factors,which in turn promotes NK cell recruitment and activation to suppress colorectal cancer growth.Furthermore,significant associations are found among low nuclear ACAT1 levels,decreased S60 phosphorylation,and reduced NK cell infiltration,as well as poor prognosis in CRC.Our findings reveal an unexpected function of ACAT1 as a nuclear acetyltransferase and elucidate its role in NK cell-dependent antitumor immunity through p50 acetylation.
文摘S.Lehrer and P.H.Rheinstein,“Alignment of Human KAT2A(GCN5)Histone Acetyltransferase and SARS-CoV-2 Orf8 Viral Proteins,”Chronic Diseases and Translational Medicine 9(2023):263–265.https://doi.org/10.1002/cdt3.56.The original article included a Conflict of Interest statement which stated:“The authors declare no conflicts of interest.”The journal and the publisher have determined that a conflict of interest on behalf of each author was not declared at publication.The journal and the publisher have had sufficient communication with the authors via email after raising questions about the Conflict of Interest in the article.The authors declared that there was no undeclared Conflict of Interest and further stated that their individual affiliations with commercial entities did not influence the research findings.
基金supported by the National Natural Science Foundation of China(32025003)the National Key Research and Development Program of China(2016YFA0500801)from the Chinese Ministry of Science and Technology。
文摘Although two Enhancer of Polycomb-like proteins,EPL1 A and EPL1 B(EPL1 A/B),are known to be conserved and characteristic subunits of the Nu A4-type histone acetyltransferase complex in Arabidopsis thaliana,the biological function of EPL1 A/B and the mechanism by which EPL1 A/B function in the complex remain unknown.Here,we report that EPL1 A/B are required for the histone acetyltransferase activity of the Nu A4 complex on the nucleosomal histone H4 in vitro and for the enrichment of histone H4 K5 acetylation at thousands of protein-coding genes in vivo.Our results suggest that EPL1 A/B are required for linking the Nu A4 catalytic subunits HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY 1(HAM1)and HAM2 with accessory subunits in the Nu A4 complex.EPL1 A/B function redundantly in regulating plant development especially in chlorophyll biosynthesis and de-etiolation.The EPL1 A/B-dependent transcription and H4 K5 Ac are enriched at genes involved in chlorophyll biosynthesis and photosynthesis.We also find that EAF6,another characteristic subunit of the Nu A4 complex,contributes to de-etiolation.These results suggest that the Arabidopsis Nu A4 complex components function as a whole to mediate histone acetylation and transcriptional activation specifically at light-responsive genes and are critical for photomorphogenesis.
文摘The mammalian MOF （male absent on the first）, a member of the MYST （MOZ, YBF2, SAS2, and Tip60） family of histone acetyltransferases （HATs）, is the major enzyme that catalyzes the acetylation of histone H4 on lysine 16. Acetylation of K16 is a prevalent mark associated with chromatin decondensation. MOF has recently been shown to play an essential role in maintaining normal cell functions. In this study, we discuss the important roles of MOF in DNA damage repair, apoptosis, and tumorigenesis. We also analyze the role of MOF as a key regulator of the core transcriptional network of embryonic stem cells.
基金the National Key Research and Development Program of China(No.2022YFD2100102)the Fundamental Research Funds for the Central Universities(No.226-2023-00152)+1 种基金the 111 Project(No.B17039)Zhejiang Provincial Cooperative Extension Project of Agricultural Key Technology(No.2022XTTGGP01),China.
文摘Histone acetyltransferase(HAT)catalyzes histone acetylation and is involved in plant growth and development and stress responses.Here,37 CitHAT genes were identifed in Citrus clementina.Their physicochemical properties,chromosomal location,gene structure,conserved domain and motif,and cis-acting elements were characterized.CitHATs were classifed into four subfamilies based on protein sequence homology,which was strongly supported by gene structure,conserved domain,and motif analysis.The cis-acting elements in gene promoter regions were predicted to be associated with the regulation of plant growth,stress resistance,and response to hormones.Phenotypic and transcriptomic analyses of citrus callus with mock treatment and HAT inhibitor treatment revealed that increased citric acid content in inhibitor treatment may be attributed to differential expression of CitPEPCK2 and CitGS2,which may be due to the hypo-acetylation of histone H3.The expression patterns of CitHATs in citrus fruit development stages showed that CitHAG11 and CitHAG28 exhibited a negative correlation with citric acid content.Our study associates the potential function of histone acetyltransferases in citrate metabolism and extends the molecular mechanism of citrate metabolism in fruits.
基金supported by the National Natural Science Foundation of China (31571321, 31171428)the National Key Research and Develepment Program of China (2016YFE0129200)+1 种基金the Institute of the Fundamental Research Funds of Shandong University (2015JC036)the Open Projects of State Key Laboratory of Molecular Oncology (SKL-KF-2017-17)
文摘When exposing to environmental stress or internal damage, such as genotoxic stress, oxidative stress, and heat stress, cells produce a series of adaptive responses called cellular stress responses. The major proteins involved in cellular stress are heat shock proteins （HSPs）.
文摘Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.
