Cognitive impairment is a complex neurodegenerative disorder,and increased homocysteine levels are recognized as a major risk factor for this condition.Epigenetic modifications,particularly histone acetylation,have be...Cognitive impairment is a complex neurodegenerative disorder,and increased homocysteine levels are recognized as a major risk factor for this condition.Epigenetic modifications,particularly histone acetylation,have been implicated in the progression of cognitive impairment;however,the mechanisms underlying hyperhomocysteinemia-induced cognitive impairment remain unclear.In this study,we developed an hyperhomocysteinemia-induced cognitive impairment model by feeding mice a high-methionine diet and conducted behavioral and molecular analyses to elucidate the mechanisms involved in cognitive impairment.Behavioral experiments revealed significant cognitive deficits and neuroinflammation accompanied by a marked decrease in histone H3 lysine 27 acetylation in the hippocampus and cortex.Furthermore,metabolomic profiling and chromatin immunoprecipitation sequencing demonstrated substantial shifts in the levels of homocysteine metabolites and identified histone H3 lysine 27 acetylation-targeted genes involved in synaptic long-term potentiation,including Gria1,Gria3,Grin2a,Grin2b,Slc1a1,Slc24a2,Ptk2b,and Src.RNA sequencing confirmed that hyperhomocysteinemia induced neurodegeneration.In vitro experiments confirmed that decreased histone H3 lysine 27 acetylation downregulates the expression of these target genes in homocysteine-treated HT-22 cells,thereby impairing synaptic plasticity.Collectively,these findings suggest that aberrant expression of long-term potentiation-related genes regulated by histone H3 lysine 27 acetylation is a key driver of hyperhomocysteinemia-induced cognitive impairment.Targeting histone H3 lysine 27 acetylation-mediated epigenetic dysregulation may be a promising therapeutic strategy,offering potential avenues for intervention in individuals with cognitive impairment and neurodegenerative disorders.展开更多
Accumulating evidence from recent studies has highlighted the critical regulatory functions of non-histone protein acetylation in rice biological processes.This review systematically synthesizes current advances in ch...Accumulating evidence from recent studies has highlighted the critical regulatory functions of non-histone protein acetylation in rice biological processes.This review systematically synthesizes current advances in characterizing the functional attributes and regulatory mechanisms of non-histone acetylation in rice,with a specific focus on its roles in regulating gene expression,modulating metabolic enzyme activities,and mediating stress responses.Emerging studies demonstrate that non-histone acetylation dynamically modulates transcription factors,metabolic enzymes,and other pivotal functional proteins to orchestrate essential physiological processes,including growth and development,photosynthetic efficiency,and environmental stress adaptation.Using mass spectrometry,gene editing,and related technologies,researchers have identified multiple acetyltransferases and deacetylases that regulate protein stability,subcellular localization,and protein-protein interactions.Despite these advances,challenges persist,such as the complexity of the acetylation regulatory networks and species-specific differences among cereal crops.Future investigations should integrate multi-omics approaches to elucidate the molecular mechanisms of this post-translational modification,thereby facilitating the development of targeted genetic engineering strategies for rice improvement.展开更多
Background:Accumulating studies have shown the important role of circular RNAs(circRNAs)in the oncogenesis and metastasis of various cancers.We previously reported that circACTN4 could bind with FUBP1 to promote tumor...Background:Accumulating studies have shown the important role of circular RNAs(circRNAs)in the oncogenesis and metastasis of various cancers.We previously reported that circACTN4 could bind with FUBP1 to promote tumorigenesis and the development of breast cancer(BC)by increasing the expression of MYC.However,its exact molecular mechanism and biological function have not been fully elucidated.Methods:Here,Circular RNA microarray analysis was conducted in 3 pairs of BC and paracancerous tissues.The expression of circACTN4 in BC cells and tissues was detected via reverse transcription‒quantitative PCR(RT‒qPCR).Cell Counting Kit-8(CCK-8),5-ethynyl-2-deoxyuridine(EdU),transwell migration,and invasion assays were performed to further detect the biological functions of circACTN4 in BC cells.Xenograft models were used to investigate the in vivo role of circACTN4.Fluorescence in situ hybridization,Chromatin immunoprecipitation(ChIP)‒qPCR,coimmunoprecipitation,fluorometric,western blot,and rescue experiments were performed to explore the mechanism of circACTN4.Results:Our results revealed that circACTN4 was highly expressed in BC cells and tissues.The upregulated expression of circACTN4 was significantly related to the T stage and TNM stage and poor prognosis of patients with BC.circACTN4 was located primarily in the nucleus of BC cells.Upregulation of circACTN4 significantly increased the proliferation,invasion,and growth of BC cells,whereas the downregulation of circACTN4 exerted the opposite effects and induced G1/S cell cycle arrest.Mechanistically,we showed that circACTN4 could upregulate the expression of MYC and that MYC might interact with TIP60 histone acetyltransferase to increase the recruitment of TIP60 to MYC target genes and histone H4 acetylation(AcH4),thus promoting the progression of the breast cancer cell cycle and tumorigenesis.Conclusion:Taken together,our findings reveal for the first time a new mechanism by which circACTN4 could promote oncogenesis and the development of BC by increasing the AcH4 of MYC target genes via TIP60.Therefore,circACTN4 could be a novel target for BC diagnosis and remedy.展开更多
Chinese bamboo flour was chemically modified by acetylation with acetic anhydride by using trichloroacetic acid as an activation agent and the optimized condition for acetylation of bamboo flour was determined as the ...Chinese bamboo flour was chemically modified by acetylation with acetic anhydride by using trichloroacetic acid as an activation agent and the optimized condition for acetylation of bamboo flour was determined as the trichloroacetic acid amount 6.0 g per 1.5-g bamboo flour, ultrasosonication duration 40 min and the reaction time 1 h at 65℃. The composition, microstructure and thermal behavior of acetylated bamboo flour were preliminarily characterized by FT-IR, DSC and SEM etc. The acetylated bamboo flour can be molded into sheets at 130℃ and 10 MPa, indicating the modified bamboo flour possesses thermalplastic performance.展开更多
Among 39 species of microbial strains,Rhodococcus sp.AS 4.1147 possessed the ability to selectively acetylate puerarin（1） at C-6 position of the glucosyl moiety.The structure of the acetylated product,6’’-O-acetyl...Among 39 species of microbial strains,Rhodococcus sp.AS 4.1147 possessed the ability to selectively acetylate puerarin（1） at C-6 position of the glucosyl moiety.The structure of the acetylated product,6’’-O-acetylpuerarin（2） was determined by the analysis of MS,NMR spectroscopic data.The isolated yield of 2 was 22.2%.展开更多
This study investigated the inhibitory effects of curcumin on proliferation of hematological malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacetylation levels. The effects of cu...This study investigated the inhibitory effects of curcumin on proliferation of hematological malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacetylation levels. The effects of curcumin and histone deacetylase inhibitor trichostatin A （TSA） on the growth of Raji cells were tested by MTT assay. The expression of acetylated histone-3 （H3） in Raji, HL60 and K562 cells, and peripheral blood mononuclear cells （PBMCs） treated with curcumin or TSA was detected by immunohistochemistry and FACS. The results showed curcumin inhibited pro- liferation of Raji cells significantly in a time- and dose-dependent fashion, while exhibited low toxicity in PBMCs. Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested. In conclusion, curcumin inhibited proliferation of Raji cells selectively, enhanced the level of acetylated H3 in Raji, HL60, and K562 cells, which acted as a histone deacetylase inhibitor like TSA. Furthermore, up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.展开更多
Histone deacetylases （HDACs） and histone acetyl transferases （HATs） are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained...Histone deacetylases （HDACs） and histone acetyl transferases （HATs） are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained in the N-terminal extensions of the core histones. Acetylation of histones affects gene expression through its influence on chromatin conformation. In addition, several non-histone proteins are regulated in their stability or biological function by the acetylation state of specific lysine residues. HDACs intervene in a multitude of biological processes and are part of a multiprotein family in which each member has its specialized functions. In addition, HDAC activity is tightly controlled through targeted recruitment, protein-protein interactions and post-translational modifications. Control of cell cycle progression, cell survival and differentiation are among the most important roles of these enzymes. Since these processes are affected by malignant transformation, HDAC inhibitors were developed as antineoplastic drugs and are showing encouraging efficacy in cancer patients.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
At relatively high cellulose mass concentrations(8%,10%,and 12%),homogeneous acetylation of cellulose was carried out in an ionic liquid,1-allyl-3-methylimidazolium chloride(AmimCl).Without using any catalyst,cellulos...At relatively high cellulose mass concentrations(8%,10%,and 12%),homogeneous acetylation of cellulose was carried out in an ionic liquid,1-allyl-3-methylimidazolium chloride(AmimCl).Without using any catalyst,cellulose acetates(CAs)with the degree of substitution(DS)in a range from 0.4 to 3.0 were synthesized in one-step.The effects of reaction time,temperature and molar ratio of acetic anhydride/anhydroglucose unit(AGU) in cellulose on DS value of CAs were investigated.The synthesized CAs were characterized by means of FT-IR, NMR,and solubility,mechanical and thermal tests.After the acetylation,the used ionic liquid AmimCl was easily recycled and reused.This study shows the potential of the homogeneous acetylation of cellulose at relatively high concentrations in ionic liquids in future industrial applications.展开更多
The catalytic application of p-toluenesulfonyl chloride for efficient acetylation of various types of alcohols and phenols with acetic anhydride in solvent-free conditions is reported.Also structurally diverse alcohol...The catalytic application of p-toluenesulfonyl chloride for efficient acetylation of various types of alcohols and phenols with acetic anhydride in solvent-free conditions is reported.Also structurally diverse alcohols were formylated using formic acid based on the use of catalytic amount of p-toluenesulfonyl chloride under solvent-free condition.The reactions were carried out in short reaction time and in good to excellent yields at room temperature.展开更多
The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol...Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.展开更多
Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein...Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.展开更多
The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among th...The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.展开更多
OBJECTIVE:To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs)gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)prote...OBJECTIVE:To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs)gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)protects blood-brain barrier(BBB)integrity in a middle cerebral artery occlusion(MCAO)rat model.METHODS:Male Sprague-Dawley rats were divided into four groups:the sham group,the MCAO group,the MCAO+EA(MEA)group,and the MCAO+EA+HAT inhibitor(HATi)group.The MCAO model was generated by blocking the middle cerebral artery.EA was applied to Baihui(GV20).Samples were collected 1 or 3 d after reperfusion.Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury.The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation(ChIP).RESULTS:Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption.The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression,but HATi reversed these effects of EA.In addition,ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter.CONCLUSION:EA treatment at Baihui(GV20)regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke,which preserves the structural integrity of the BBB in MCAO rats.These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.展开更多
The understanding of mechanisms leading to cellular differentiation is the main aim of numerous studies.Accessibility of DNA to transcription factors depends on local chromatin structure and chromatin compaction inhib...The understanding of mechanisms leading to cellular differentiation is the main aim of numerous studies.Accessibility of DNA to transcription factors depends on local chromatin structure and chromatin compaction inhibits gene transcription.Histone acetylation correlates with an open chromatin structure and increased gene expression.Gene transcription levels are changed in early embryonic stem cells differentiation in a tissuespecific manner and epigenetic marks are modified,including increased global acetylation levels.Manipulation of histone deacetylases activity might be an interesting tool to generate populations of specific cell types for transplantation purposes.Thus,this review aims to show recent findings on histone acetylation,a post translational modif ication and its manipulation in embryonic stem cells differentiation.展开更多
A variety of alcohols and phenols are efficiently acetylated with acetic anhydride in the presence of a catalytic amount of V（HSO4）3 in solution and under solvent free conditions. Mild reaction conditions, high yiel...A variety of alcohols and phenols are efficiently acetylated with acetic anhydride in the presence of a catalytic amount of V（HSO4）3 in solution and under solvent free conditions. Mild reaction conditions, high yields of the products, easy procedure and selective acetylation of alcohols and phenols in the presence of amines and thiols are the main advantages of this procedure.展开更多
DNA methylation and histone acetylation can be modified by various pathological or physiological factors such as hypoxia,thus influencing gene expression.In this study,we investigated the changes of global DNA methyla...DNA methylation and histone acetylation can be modified by various pathological or physiological factors such as hypoxia,thus influencing gene expression.In this study,we investigated the changes of global DNA methylation and histone acetylation and the related enzymes in rat brain after chronic cerebrovascular hypoperfusion by bilateral common carotid occlusion（2-VO） surgery.Colorimetric and immunohistochemistry staining were used to evaluate the global DNA methylation and histone acetylation levels,respectively.The expressions of DNA methyltransferase 1/3a（DNMT1/3a）,methyl-CpG binding domain protein 2（MBD2）,histone deacetylase 3（HDAC3） and acetyltransferase（HAT） were assessed by Western blot.We found that the level of global DNA methylation was decreased to 31.7%（P ＆lt;0.01） of the sham-operated group at 10 days and increased by 30%（P ＆lt;0.01） compared with the sham group at 90 days after 2-VO surgery.DNMT3a expression was down-regulated to 75.7% of the sham group,while MBD2 expression was up-regulated by 95% compared with sham group at 90 days after 2-VO.The histone H3 acetylation level was markedly decreased to 75.3% of the sham group at 10 days and 73.5% at 90 days after 2-VO,while no significant change was found for histone H4 acetylation.HDAC3 expression was markedly down-regulated to 36% of the sham group,whereas cAMP-response element binding protein expression was up-regulated by 33.6% compared with the sham group at 90 days after 2-VO.These results suggest that chronic cerebrovascular hypoperfusion influences global DNA methylation and histone acetylation levels through the related enzymes,and therefore might contribute to several neurodegenerative diseases.展开更多
The pharmacokinetic profi les and sulfamethoxazole(SMX) acetylation process in turbot reared at 18°C were investigated. Either SMX(parent drug) or its acetylized metabolite, N4-acetylsulfamethoxazole(Ac SMX), was...The pharmacokinetic profi les and sulfamethoxazole(SMX) acetylation process in turbot reared at 18°C were investigated. Either SMX(parent drug) or its acetylized metabolite, N4-acetylsulfamethoxazole(Ac SMX), was administered intravascularly to turbot at a dosage of 50 mg/kg BW. Serum concentrations of the parent drug and its metabolite were both measured by HPLC, and the changes in concentration over time were analyzed in two- and non-compartment models because SMX treatment produced multiple peaks. The results demonstrated that the elimination half-life of the parent drugs, SMX and Ac SMX, were 159.2 and 5.9 h, respectively. The apparent volume of distribution was 0.2 and 0.8 L/kg, and the clearance was 0.038 and 0.222 L/(h·kg), for SMX and Ac SMX, respectively. SMX acetylation in turbot was 2.8%, and the deacetylation of Ac SMX was 0.2%. These fi ndings may be useful in optimizing SMX dosage regimens in turbot aquaculture.展开更多
Cutaneous melanoma is one of the most aggressive forms of skin cancer. Arctigenin, one of the major bioactive compo-nents of Arctii Fructus, has been reported to exhibit antioxidant, antitumor and anti-inflammatory ac...Cutaneous melanoma is one of the most aggressive forms of skin cancer. Arctigenin, one of the major bioactive compo-nents of Arctii Fructus, has been reported to exhibit antioxidant, antitumor and anti-inflammatory activities. In the pre-sent study, we investigated the effect of arctigenin on induction of apoptosis in highly metastatic SK-MEL-28 human melanoma cells. Arctigenin inhibited growth of SK-MEL-28 cells in a dose-dependent manner. Treatment of SK-MEL-28cells with arctigenin caused cleavage of caspases 3, 7 and 9, and poly (ADP-ribose) polymerase in a dose-dependent manner. Furthermore, acetylation of histone H3 and H4 in the SK-MEL-28 cells was dramatically increased by arctigenin treatment. Collectively, these findings indicate that arctigenin-induces apoptosis of SK-MEL-28 melanoma cells via activation of caspases and histone acetylation.展开更多
基金supported by the Science Research Start-up Fund for Doctor of Shanxi Medical University,No.SD2114(to JL).
文摘Cognitive impairment is a complex neurodegenerative disorder,and increased homocysteine levels are recognized as a major risk factor for this condition.Epigenetic modifications,particularly histone acetylation,have been implicated in the progression of cognitive impairment;however,the mechanisms underlying hyperhomocysteinemia-induced cognitive impairment remain unclear.In this study,we developed an hyperhomocysteinemia-induced cognitive impairment model by feeding mice a high-methionine diet and conducted behavioral and molecular analyses to elucidate the mechanisms involved in cognitive impairment.Behavioral experiments revealed significant cognitive deficits and neuroinflammation accompanied by a marked decrease in histone H3 lysine 27 acetylation in the hippocampus and cortex.Furthermore,metabolomic profiling and chromatin immunoprecipitation sequencing demonstrated substantial shifts in the levels of homocysteine metabolites and identified histone H3 lysine 27 acetylation-targeted genes involved in synaptic long-term potentiation,including Gria1,Gria3,Grin2a,Grin2b,Slc1a1,Slc24a2,Ptk2b,and Src.RNA sequencing confirmed that hyperhomocysteinemia induced neurodegeneration.In vitro experiments confirmed that decreased histone H3 lysine 27 acetylation downregulates the expression of these target genes in homocysteine-treated HT-22 cells,thereby impairing synaptic plasticity.Collectively,these findings suggest that aberrant expression of long-term potentiation-related genes regulated by histone H3 lysine 27 acetylation is a key driver of hyperhomocysteinemia-induced cognitive impairment.Targeting histone H3 lysine 27 acetylation-mediated epigenetic dysregulation may be a promising therapeutic strategy,offering potential avenues for intervention in individuals with cognitive impairment and neurodegenerative disorders.
基金supported by the Project of Zhongshan Biological Breeding Laboratory,China(Grant Nos.ZSBBL-KY2024-01 and ZSBBL-KY2025-2)the Key R&D Program of Jiangsu Province,China(Grant No.BE2022335)the Fund of Priority Academic Program Development of Jiangsu Higher Education Institutions,China.
文摘Accumulating evidence from recent studies has highlighted the critical regulatory functions of non-histone protein acetylation in rice biological processes.This review systematically synthesizes current advances in characterizing the functional attributes and regulatory mechanisms of non-histone acetylation in rice,with a specific focus on its roles in regulating gene expression,modulating metabolic enzyme activities,and mediating stress responses.Emerging studies demonstrate that non-histone acetylation dynamically modulates transcription factors,metabolic enzymes,and other pivotal functional proteins to orchestrate essential physiological processes,including growth and development,photosynthetic efficiency,and environmental stress adaptation.Using mass spectrometry,gene editing,and related technologies,researchers have identified multiple acetyltransferases and deacetylases that regulate protein stability,subcellular localization,and protein-protein interactions.Despite these advances,challenges persist,such as the complexity of the acetylation regulatory networks and species-specific differences among cereal crops.Future investigations should integrate multi-omics approaches to elucidate the molecular mechanisms of this post-translational modification,thereby facilitating the development of targeted genetic engineering strategies for rice improvement.
基金supported by National Natural Science Foundation of China(No.82173170,Junxia ChenNo.82103089,Lei Xing)Natural Science Foundation of Chongqing,China(No.CSTB2022BSXMJCX0057,Lei Xing).
文摘Background:Accumulating studies have shown the important role of circular RNAs(circRNAs)in the oncogenesis and metastasis of various cancers.We previously reported that circACTN4 could bind with FUBP1 to promote tumorigenesis and the development of breast cancer(BC)by increasing the expression of MYC.However,its exact molecular mechanism and biological function have not been fully elucidated.Methods:Here,Circular RNA microarray analysis was conducted in 3 pairs of BC and paracancerous tissues.The expression of circACTN4 in BC cells and tissues was detected via reverse transcription‒quantitative PCR(RT‒qPCR).Cell Counting Kit-8(CCK-8),5-ethynyl-2-deoxyuridine(EdU),transwell migration,and invasion assays were performed to further detect the biological functions of circACTN4 in BC cells.Xenograft models were used to investigate the in vivo role of circACTN4.Fluorescence in situ hybridization,Chromatin immunoprecipitation(ChIP)‒qPCR,coimmunoprecipitation,fluorometric,western blot,and rescue experiments were performed to explore the mechanism of circACTN4.Results:Our results revealed that circACTN4 was highly expressed in BC cells and tissues.The upregulated expression of circACTN4 was significantly related to the T stage and TNM stage and poor prognosis of patients with BC.circACTN4 was located primarily in the nucleus of BC cells.Upregulation of circACTN4 significantly increased the proliferation,invasion,and growth of BC cells,whereas the downregulation of circACTN4 exerted the opposite effects and induced G1/S cell cycle arrest.Mechanistically,we showed that circACTN4 could upregulate the expression of MYC and that MYC might interact with TIP60 histone acetyltransferase to increase the recruitment of TIP60 to MYC target genes and histone H4 acetylation(AcH4),thus promoting the progression of the breast cancer cell cycle and tumorigenesis.Conclusion:Taken together,our findings reveal for the first time a new mechanism by which circACTN4 could promote oncogenesis and the development of BC by increasing the AcH4 of MYC target genes via TIP60.Therefore,circACTN4 could be a novel target for BC diagnosis and remedy.
基金Fujian Province science and technology office (2007F5030)(in part) National Natural Scince Foundation of China (grant 50473063)
文摘Chinese bamboo flour was chemically modified by acetylation with acetic anhydride by using trichloroacetic acid as an activation agent and the optimized condition for acetylation of bamboo flour was determined as the trichloroacetic acid amount 6.0 g per 1.5-g bamboo flour, ultrasosonication duration 40 min and the reaction time 1 h at 65℃. The composition, microstructure and thermal behavior of acetylated bamboo flour were preliminarily characterized by FT-IR, DSC and SEM etc. The acetylated bamboo flour can be molded into sheets at 130℃ and 10 MPa, indicating the modified bamboo flour possesses thermalplastic performance.
基金The Science & Technology Project of Guangdong Province (Grant No. 2011A080403020)the Program for New Century Excellent Talents in University (Grant No. NCET-06-0155)
文摘Among 39 species of microbial strains,Rhodococcus sp.AS 4.1147 possessed the ability to selectively acetylate puerarin（1） at C-6 position of the glucosyl moiety.The structure of the acetylated product,6’’-O-acetylpuerarin（2） was determined by the analysis of MS,NMR spectroscopic data.The isolated yield of 2 was 22.2%.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30271672).
文摘This study investigated the inhibitory effects of curcumin on proliferation of hematological malignant cells in vitro and the anti-tumor mechanism at histone acetylation/histone deacetylation levels. The effects of curcumin and histone deacetylase inhibitor trichostatin A （TSA） on the growth of Raji cells were tested by MTT assay. The expression of acetylated histone-3 （H3） in Raji, HL60 and K562 cells, and peripheral blood mononuclear cells （PBMCs） treated with curcumin or TSA was detected by immunohistochemistry and FACS. The results showed curcumin inhibited pro- liferation of Raji cells significantly in a time- and dose-dependent fashion, while exhibited low toxicity in PBMCs. Curcumin induced up-regulation of the expression of acetylated H3 dose-dependently in all malignant cell lines tested. In conclusion, curcumin inhibited proliferation of Raji cells selectively, enhanced the level of acetylated H3 in Raji, HL60, and K562 cells, which acted as a histone deacetylase inhibitor like TSA. Furthermore, up-regulation of H3 acetylation may play an important role in regulating the proliferation of Raji cells.
文摘Histone deacetylases （HDACs） and histone acetyl transferases （HATs） are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained in the N-terminal extensions of the core histones. Acetylation of histones affects gene expression through its influence on chromatin conformation. In addition, several non-histone proteins are regulated in their stability or biological function by the acetylation state of specific lysine residues. HDACs intervene in a multitude of biological processes and are part of a multiprotein family in which each member has its specialized functions. In addition, HDAC activity is tightly controlled through targeted recruitment, protein-protein interactions and post-translational modifications. Control of cell cycle progression, cell survival and differentiation are among the most important roles of these enzymes. Since these processes are affected by malignant transformation, HDAC inhibitors were developed as antineoplastic drugs and are showing encouraging efficacy in cancer patients.
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.
基金Supported by the National Basic Research Program of China(2009CB219901)
文摘At relatively high cellulose mass concentrations(8%,10%,and 12%),homogeneous acetylation of cellulose was carried out in an ionic liquid,1-allyl-3-methylimidazolium chloride(AmimCl).Without using any catalyst,cellulose acetates(CAs)with the degree of substitution(DS)in a range from 0.4 to 3.0 were synthesized in one-step.The effects of reaction time,temperature and molar ratio of acetic anhydride/anhydroglucose unit(AGU) in cellulose on DS value of CAs were investigated.The synthesized CAs were characterized by means of FT-IR, NMR,and solubility,mechanical and thermal tests.After the acetylation,the used ionic liquid AmimCl was easily recycled and reused.This study shows the potential of the homogeneous acetylation of cellulose at relatively high concentrations in ionic liquids in future industrial applications.
文摘The catalytic application of p-toluenesulfonyl chloride for efficient acetylation of various types of alcohols and phenols with acetic anhydride in solvent-free conditions is reported.Also structurally diverse alcohols were formylated using formic acid based on the use of catalytic amount of p-toluenesulfonyl chloride under solvent-free condition.The reactions were carried out in short reaction time and in good to excellent yields at room temperature.
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
基金supported by the National Key Basic Research and Development Program(NKBRDP)of China(No.2009CB522000)the National Natural Science Foundation of China(No.30971050)+1 种基金the State Key Program of the National Natural Science of China(No.81130020)the Key Program on Basic Science of Henan Science and Technology Department(No.094200510005)
文摘Previous reports showed that decreased histone deacetylase activity significantly potentiated the rewarding effects of psychostimulants, and that encoding of the 5-HT3 receptor by the htr3a gene was related to ethanol-seeking behavior. However, the effects of a histone deacetylase inhibitor on ethanol-seeking behavior and epigenetic regulation of htr3a mRNA expression after chronic ethanol exposure are not fully understood. Using quantitative reverse transcription-polymerase chain reaction and chromatin immunoprecipitation analysis, we investigated the effects of chronic ethanol exposure and its interaction with a histone deacetylase inhibitor on histone-acetylation-mediated changes in htr3a mRNA expression in the htr3a promoter region. The conditioned place preference procedure was used to evaluate ethanol-seeking behavior. Chronic exposure to ethanol effectively elicited place conditioning. In the prefrontal cortex, the acetylation of H3K9 and htr3a mRNA expression in the htr3a promoter region were significantly higher in the ethanol group than in the saline group. The histone deacetylase inhibitor sodium butyrate potentiated the effects of ethanol on htr3a mRNA expression and enhanced ethanol-induced conditioned place preferences. These results suggest that ethanol upregulates htr3a levels through mechanisms involving H3K9 acetylation, and that histone acetylation may be a therapeutic target for treating ethanol abuse.
基金Supported by The National Institute of Alcohol Abuse and Alcoholism (R21 AA015683) awarded to P.L.T.
文摘Although the clinical manifestations of alcoholic liver disease are well-described, little is known about the molecular basis of liver injury. Recent studies have indicated that ethanol exposure induces global protein hyperacetylationo This reversible, post- translational modification on the E-amino groups of lysine residues has been shown to modulate multiple, diverse cellular processes ranging from transcriptional activation to microtubule stability. Thus, alcohol- induced protein hyperacetylation likely leads to major physiological consequences that contribute to alcohol-induced hepatotoxicity. Lysine acetylation is controlled by the activities of two opposing enzymes, histone acetyltransferases and histone deacetylases. Currently, efforts are aimed at determining which enzymes are responsible for the increased acetylation of specific substrates. However, the greater challenge will be to determine the physiological ramifications of protein hyperacetylation and how they might contribute to the progression of liver disease. In this review, we will first list and discuss the proteins known to be hyperacetylated in the presence of ethanol. We will then describe what is known about the mechanisms leading to increased protein acetylation and how hyperacetylation may perturb hepatic function.
文摘The HIV-1 LTR controls the expression of HIV-1 viral genes and thus is critical for viral propagation and pathology. Numerous host factors have been shown to participate in the regulation of the LTR promoter. Among them is the thyroid hormone (T3) receptor (TR). TR has been shown to bind to the critical region of the promoter that contain the NFbB and Sp1 binding sites. Interestingly, earlier transient transfection studies in tissue culture cells have yielded contradicting conclusions on the role of TR in LTR regulation, likely due to the use of different cell types and/or lack of proper chromatin organization. Here, using the frog oocyte as a model system that allows replication-coupled chromatin assembly, mimicking that in somatic cells, we demonstrate that unliganded heterodimers of TR and RXR (9-cis retinoic acid receptor) repress LTR while the addition of T3 relieves the repression and further activates the promoter. More importantly, we show that chromatin and unliganded TR/RXR synergize to repress the promoter in a histone deacetylase-dependent manner.
基金the National Natural Science Foundation of China:the Role of Intestinal Flora-Treg/γδT Cell-IL-17 Signaling in the Neuroprotective Effect of Electroacupuncture on Ischemic Brain Injury(No.81774403)the Natural Science Foundation of the Jiangsu Province of China:Study on the Mechanism of Acupuncture Antistroke Immune Inflammatory Response Based on Intestinal Treg/γδT Cell-IL-17 Signaling Pathway(No.BK20171492)+2 种基金the Postgraduate Scientific Research Innovation Practice Project of the Jiangsu Province of China:a Study based on the Butyric Acid-HDAC-Foxp3 Pathway to Explore the Regulatory Effect of Acupuncture on Intestinal Treg in Rats with Stroke(No.KYCX21_1715)a Study on the Anti-brain Injury of Electroacupuncture Based on Intestinal Microbiota-Treg/γδT Cell-IL-17 Pathway(No.KYCX21_1716)the Key University Science Research Project of Jiangsu Province:the Role of Preactivation of the Treg Immune Response in the Mechanism of Anti-stroke Neuroinflammatory Response in Acupuncture Pretreatment(No.22KJA360003)。
文摘OBJECTIVE:To explore whether the regulation of matrix metalloproteinase 9(MMP-9)/tissue inhibitors of MMPs(TIMPs)gene expression through histone acetylation is a possible mechanism by which electroacupuncture(EA)protects blood-brain barrier(BBB)integrity in a middle cerebral artery occlusion(MCAO)rat model.METHODS:Male Sprague-Dawley rats were divided into four groups:the sham group,the MCAO group,the MCAO+EA(MEA)group,and the MCAO+EA+HAT inhibitor(HATi)group.The MCAO model was generated by blocking the middle cerebral artery.EA was applied to Baihui(GV20).Samples were collected 1 or 3 d after reperfusion.Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury.The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and chromatin immunoprecipitation(ChIP).RESULTS:Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption.The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression,but HATi reversed these effects of EA.In addition,ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter.CONCLUSION:EA treatment at Baihui(GV20)regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke,which preserves the structural integrity of the BBB in MCAO rats.These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.
文摘The understanding of mechanisms leading to cellular differentiation is the main aim of numerous studies.Accessibility of DNA to transcription factors depends on local chromatin structure and chromatin compaction inhibits gene transcription.Histone acetylation correlates with an open chromatin structure and increased gene expression.Gene transcription levels are changed in early embryonic stem cells differentiation in a tissuespecific manner and epigenetic marks are modified,including increased global acetylation levels.Manipulation of histone deacetylases activity might be an interesting tool to generate populations of specific cell types for transplantation purposes.Thus,this review aims to show recent findings on histone acetylation,a post translational modif ication and its manipulation in embryonic stem cells differentiation.
基金this work by the research affair,University of Guilan,Rasht,Iran,
文摘A variety of alcohols and phenols are efficiently acetylated with acetic anhydride in the presence of a catalytic amount of V（HSO4）3 in solution and under solvent free conditions. Mild reaction conditions, high yields of the products, easy procedure and selective acetylation of alcohols and phenols in the presence of amines and thiols are the main advantages of this procedure.
基金supported by the National Natural Science Foundation of China(8107092)the Beijing Education Committee of Science and Technology Plan Projects(KM201110025006)the China 973 Preprogram(2011CB512109)
文摘DNA methylation and histone acetylation can be modified by various pathological or physiological factors such as hypoxia,thus influencing gene expression.In this study,we investigated the changes of global DNA methylation and histone acetylation and the related enzymes in rat brain after chronic cerebrovascular hypoperfusion by bilateral common carotid occlusion（2-VO） surgery.Colorimetric and immunohistochemistry staining were used to evaluate the global DNA methylation and histone acetylation levels,respectively.The expressions of DNA methyltransferase 1/3a（DNMT1/3a）,methyl-CpG binding domain protein 2（MBD2）,histone deacetylase 3（HDAC3） and acetyltransferase（HAT） were assessed by Western blot.We found that the level of global DNA methylation was decreased to 31.7%（P ＆lt;0.01） of the sham-operated group at 10 days and increased by 30%（P ＆lt;0.01） compared with the sham group at 90 days after 2-VO surgery.DNMT3a expression was down-regulated to 75.7% of the sham group,while MBD2 expression was up-regulated by 95% compared with sham group at 90 days after 2-VO.The histone H3 acetylation level was markedly decreased to 75.3% of the sham group at 10 days and 73.5% at 90 days after 2-VO,while no significant change was found for histone H4 acetylation.HDAC3 expression was markedly down-regulated to 36% of the sham group,whereas cAMP-response element binding protein expression was up-regulated by 33.6% compared with the sham group at 90 days after 2-VO.These results suggest that chronic cerebrovascular hypoperfusion influences global DNA methylation and histone acetylation levels through the related enzymes,and therefore might contribute to several neurodegenerative diseases.
基金Supported by the National Natural Science Foundation of China(No.31101298)the Special Scientifi c Research Funds for Central Non-Profi t Institutes,Chinese Academy of Fishery Sciences(No.2014A09XK02)partially by the Independent Innovation Foundation of Shandong Province(No.2013CXC80202)
文摘The pharmacokinetic profi les and sulfamethoxazole(SMX) acetylation process in turbot reared at 18°C were investigated. Either SMX(parent drug) or its acetylized metabolite, N4-acetylsulfamethoxazole(Ac SMX), was administered intravascularly to turbot at a dosage of 50 mg/kg BW. Serum concentrations of the parent drug and its metabolite were both measured by HPLC, and the changes in concentration over time were analyzed in two- and non-compartment models because SMX treatment produced multiple peaks. The results demonstrated that the elimination half-life of the parent drugs, SMX and Ac SMX, were 159.2 and 5.9 h, respectively. The apparent volume of distribution was 0.2 and 0.8 L/kg, and the clearance was 0.038 and 0.222 L/(h·kg), for SMX and Ac SMX, respectively. SMX acetylation in turbot was 2.8%, and the deacetylation of Ac SMX was 0.2%. These fi ndings may be useful in optimizing SMX dosage regimens in turbot aquaculture.
文摘Cutaneous melanoma is one of the most aggressive forms of skin cancer. Arctigenin, one of the major bioactive compo-nents of Arctii Fructus, has been reported to exhibit antioxidant, antitumor and anti-inflammatory activities. In the pre-sent study, we investigated the effect of arctigenin on induction of apoptosis in highly metastatic SK-MEL-28 human melanoma cells. Arctigenin inhibited growth of SK-MEL-28 cells in a dose-dependent manner. Treatment of SK-MEL-28cells with arctigenin caused cleavage of caspases 3, 7 and 9, and poly (ADP-ribose) polymerase in a dose-dependent manner. Furthermore, acetylation of histone H3 and H4 in the SK-MEL-28 cells was dramatically increased by arctigenin treatment. Collectively, these findings indicate that arctigenin-induces apoptosis of SK-MEL-28 melanoma cells via activation of caspases and histone acetylation.
