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Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated Histone acetylation modification in weaning piglets

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Journal of Animal Science and Biotechnology 2023年第2期14卷 792-805页

作者： Qiufang Zong Huan Qu Yahui Zhao Haoyu Liu Shenglong Wu Shuai Wang Wenbin Bao Demin Cai College of Animal Science and Technology Yangzhou UniversityYangzhou 225009PR China Joint International Research Laboratory of Agriculture&Agri‑Product Safety Yangzhou UniversityYangzhou 225009PR China Department of Animal Nutrition and Feed Science College of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070PR China.

Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic Histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent

关键词： Cholesterol biosynthesis DON Histone acetylation RORγ Sodium butyrate

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Dynamic profiles of DNA methylation and the interaction with Histone acetylation during fiber cell initiation of Gossypium hirsutum

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Journal of Cotton Research 2022年第1期5卷 34-47页

作者： CHEN Guangyu LI Yonghui WEI Zhenzhen GAN Lei LIU Jisheng WANG Zhi Zhengzhou Research Base State Key Laboratory of Cotton BiologySchool of Agricultural SciencesZhengzhou UniversityZhengzhou 450001China Institute of Cotton Research Chinese Agricultural Academy of SciencesAnyang 455000China

Background:Fiber,as the main product of cotton,provides main raw material for the textile industry.Many key factors have been revealed a significant role in fiber cell development including Myb proteins,phytohormones,fatty acid metabolites,and epigenetic modifications.DNA methylation is one of the important epigenetic modifications to regulate plant development and responses to abiotic or biotic stimuli.In general,DNA methylation consisting of 5mC and 6mA regulates the chromatin structure and gene transcription to affect plant development,however,the detailed role and underlying mechanism of DNA methylation in the fiber development of cotton are yet vague.Results:Here,systematical study of the 5mC and 6mA DNA methylation profiles during the fiber initiation period of Xu142 and its glabrous mutant Xu142fl represented a clear alteration of global DNA methylation associated with fiber cell initiation.Then,the genome-wide identification of genes responsible for methylation regulation at the fifth carbon of cytosine and the sixth carbon of adenine of DNA was operated in Gossypium hirsutum.As a result,13,10,6,and 17 genes were identified for 5mC methylation,5mC demethylation,6mA methylation,and 6mA demethylation,respectively.We then investigated the tissue expression pattern of all these genes,and some genes showed higher expression levels in fiber initiation,among which some displayed a significant change in transcription between Xu142 and Xu142fl.The possible interaction between Histone acetylation and DNA methylation in fiber initiation through in vitro culture was studied by dot blot,and the results showed that repressed histone deacetylation by Trichostatin A(TSA)inhibited the global DNA methylation,and some causal genes(e.g.,GhDMT13,GhDAMT2,GhALKBH12,GhDM7)were also identified.Conclusions:In this study,all the findings indicated the interplay between Histone acetylation and DNA methylation,supporting their important roles and providing precious clues for the epigenetic modifications associated with DNA methylatio

关键词： Fiber initiation DNA methylation Histone acetylation Gossypium hirsutum

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Chronic cerebrovascular hypoperfusion affects global DNA methylation and Histone acetylation in rat brain

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Neuroscience Bulletin 2013年第6期29卷 685-692页

作者： Xiangmei Wu Jing Sun Liang Li Department of Pathology Capital Medical University

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.

关键词： cerebrovascular hypoperfusion global DNA methylation Histone acetylation rat

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Histone acetylation of the htr3a gene in the prefrontal cortex of Wistar rats regulates ethanol-seeking behavior

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Neural Regeneration Research 2012年第13期7卷 1021-1028页

作者： Yahui Xu Xuebing Liu Xiaojie Zhang Guanbai Zhang Ruiling Zhang Tieqiao Liu Wei Hao Mental Health Institute Second Xiangya Hospital Central South University Changsha 410011 Hunan Province China Townsend Family Laboratories Graduate Program in Neuroscience University of British Columbia 2255 Wesbrook Mall Vancouver B. C V6T 1Z3 Canada Second Affiliated Hospital of Xinxiang Medical University Xinxiang 453003 Henan Province China

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.

关键词： Ethanol seeking chronic ethanol exposure htr3a histone deacetylase Histone acetylation sodiumbutyrate neural regeneration

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The secondary laticifer differentiation in rubber tree is induced by trichostatin A, an inhibitor of Histone acetylation

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Frontiers of Agricultural Science and Engineering 2016年第4期3卷 357-362页

作者： Shixin ZHANG Shaohua WU Weimin TIAN Key Laboratory of Biology and Genetic Resources of Rubber Tree Ministry of Agriculture State Key Laboratory Incubation Base for Cultivation and Physiology of Tropical Crops Rubber Research InstituteChinese Academy of Tropical Agricultural Sciences

The secondary laticifer, a specific tissue in the secondary phloem of rubber tree, is differentiated from the vascular cambia. The number of the secondary laticifer in the trunk bark of rubber tree is positively correlated with rubber yield. Although jasmonates have been demonstrated to be crucial in the regulation of secondary laticifer differentiation, the mechanism for the jasmonate-induced secondary laticifer differentiation remains to be elucidated.By using an experimental morphological technique, the present study revealed that trichostatin A(TSA), an inhibitor of histone deacetylation, could induce the secondary laticifer differentiation in a concentrationdependent manner. The results suggest that Histone acetylation is essential for the secondary laticifer differentiation in rubber tree.

关键词： Hevea brasiliensis Histone acetylation laticifer differentiation trichostatin vascular cambia

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Effects of Triptolide on Histone acetylation and HDAC8 Expression in Multiple Myeloma in vitro

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Chinese Journal of Cancer Research 2010年第2期22卷 148-155页

作者： Fei Zhao Ling-lan Zeng Yan Chen Rui Li Yuan Liu Lu Wen Yi-quan Cheng Chun Zhang Department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Objective： Multiple myeloma is a kind of malignant plasma cell disease that originated from B lymphocyte and secrete great amount of monoclonal immunoglobulin. It is still one of the refractory diseases at present. Numerous studies show that there is an intensive relationship between the disequilibrium of Histone acetylation and the occurance of multiple myeloma. Here we investigated the effect of triptolide（TPL） on the proliferation, apoptosis, histone H3 and H4 acetylation and expression of histone deacetylase 8 （HDAC8） in vitro, to explore its anti- myeloma mechanism. Methods： The effect of triptolide on the growth of RPMI8226 was studied by 3-（4,5-Dimethyl-2-thiazolyl） -2,5-diphenyl-2H-tetrazolium（MTT） assay. Apoptosis was detected by Hoechst 33258 staining. The protein expressions of acetyl-histone H3 and H4 were determined by Western blot, and the expression of HDAC8 was assessed by RT-PCR, Western blot and confocal microscopy. Results： Triptolide inhibited the proliferation of RPMI8226 and induced apoptosis in a time- and dosedependent manner. The 36h IC50 value was （105.370 ± 0.189）nmol/L. Triptolide increased the acetylation of histone H3 and H4 greatly. Furthermore, triptolide significantly down-regulated the mRNA and protein expression of HDAC8. Conclusion： Triptolide can inhibit proliferation and induce apoptosis of RPMI8226 significantly. Triptolide reduces the expression of HDAC8 in order to increase the histone H3 and H4 acetylation, which is possibly the anti-myeloma mechanism of triptolide.

关键词： Triptolide Histone acetylation HDAC8 Multiple myeloma

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Curcumin-induced Histone acetylation in Malignant Hematologic Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第1期29卷 25-28页

作者：胡俊斌王妍陈燕 Institute of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Intensive Care Unit Emergency Department Nanjing Drum Tower Hospital

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.

关键词： curcumin Histone acetylation histone deacetylation

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Diallyl disulfide suppresses growth of HL-60 cell through increasing his-tone acetylation and p21WAF1expression in vivo and in vitro

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Acta Pharmacologica Sinica 2006年第11期27卷 1459-1466页

作者： Jie ZHAO~(2,3)Wei-guo HUANG~2 Jie HE~2 Hui TAN~2 Qian-jin LIAO~2 Qi SU~(2,4)2 Cancer Research Institute,Nanhua University,Hengyang 421001,China 3 Department of Pathology,Mawangdui Hospital,Changsha 410016.China CancerResearchInstitute NanhuaUniversityHengyang421001China DepartmentofPathology MawangduiHospitalChangsha410016China

Aim:To examine the differentiation induction and growth inhibition of HL-60 cellsby diallyl disulfide(DADS),and its relationship with the alterations of histoneacetylation and p21WAF1expression in vitro and in vivo.Methods:Differentiationwas studied by nitroblue tetrazolium(NBT)reduction of HL-60 cell in vitro.HL-60cells 5×10~6 were injected into the right side of the peritoneal cavity of severecombined immunodeficiency(SCID)mice.When the peritoneal neoplasms weredetected,the SCID mice were randomly divided into 3 groups and received an ipinjection of vehicle alone(NS),DADS or sodium butyrate(SB).The growthinhibition of peritoneal neoplasms induced by DADS was observed by a growthcurve.The cycle distribution of HL-60 cells in SCID mice was monitored by flowcytometry.The expression of acetylated histone H3,H4 and p21WAF1were mea-sured by Western blot.Results:After treatment with DADS for 0-72 h,the NBTreduction ability of HL-60 cells increased in a time-dependent manner,comparedwith no treatment of HL-60 cells.In the HL-60 cells treated with DADS for 24 h,theexpression of acetylated histone H3,H4,and p21WAF1increased obviously.Aftertreatment with DADS,tumor growth was markedly suppressed.HL-60 cells frommice treated with DADS were blocked in the G1phase,from 25.4% to 63.4%.Thetumors from the mice treated with DADS showed an increase of acetylated his-tone H3,H4,and p21WAF1.Conclusion:DADS could induce differentiation andinhibit the growth of HL-60 cells through increasing the expression of acetylatedhistone H3,I44,and p21WAF1in vitro and in vivo.

关键词： diallyl disulfide leukemia growth inhibition Histone acetylation p21WAF1

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The wheat elongator subunit 4 positively regulates immune responses through facilitating chromatin Histone acetylation

The wheat elongator subunit 4 positively regulates immune re...

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第十届全国小麦基因组学及分子育种大会

作者： Kai Wang Zengyan Zhang The National Key Facility for Crop Gene Resources and Genetic Improvement Key Laboratory of Biology and Genetic Improvement of Triticeae CropsMinistry of AgricultureInstitute of Crop ScienceChinese Academy of Agricultural Sciences

Arabidopsis Elongator complex,composed of six subunits,has been implicated in growth,development,and innate immunity.However,there have no experimental evidences for Elongator subunit 4 regulates chromatin Histone acetylation and transcription of defense genes.Wheat(Triticum aestivum) is necessary for global food security.Yet,roles of wheat Elongator have unknown.Here,we report wheat Elongator subunit 4 involved in immune responses and chromatin Histone acetylation TaELP4 transcription was induced upon infection of an important fungal pathogen Rhizoctonia cerealis and associated with the resistance degree of wheat.TaELP4-silenced wheat plants displayed significantly impaired-resistance to R.cereals Silencing of TaELP4 significantly repressed chromatin Histone acetylation levels of a subset of defense-related genes in wheat,such as TaAGC1,TaCPK7-D,TaPAL5,Defensin,Chitinase2,and TaELP2,and thereby decreased their transcripts.Conversely,ectopic expression of TaELP4 significantly promoted chromatin Histone acetylation of AtPDF1.2,Chitinase,and AtELP2,and increased their transcripts in Arabidopsis,ultimately,enhanced plant resistance against Botrytis einerea.Collectively,TaELP4 positively regulates immune responses of wheat and Arabidopsis to R.cerealis and B cinerea through heightening chromatin Histone acetylation of defense-related genes and increasing their transcripts.Our study provides novel insights on roles of wheat Elongator and ELP4-triggering transcriptome reprogramming via Histone acetylation.

关键词： Triticum aestivum Elongator subunit 4 Histone acetylation disease resistance Rhizoctonia cerealis

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Involvement of chromatin and Histone acetylation in the regulation of HIV-LTR by thyroid hormone receptor

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Cell Research 2001年第1期11卷 8-16页

作者： SHAO CHUNG VICTOR HSIA, HUA WANG, YUN BO SHI (Unit on Molecular Morphogenesis, Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, National Institute of Health, Building 18T, Room 106, Bethesda, MD 20892-5431, USA 1Unit on Molecular Morphogenesis Laboratory of Molecular Embryology National Institute of Child Health and Human Development National Institute of Health Building 18T Room 106 Bethesda MD 20892-5431 USA 1Unit on Molecular Morphogenesis Laboratory of Molecular Embryology National Institute of Child Health and Human Development National Institute of Health Building 18T Room 106 Bethesda MD 20892-5431 USA 1Unit on Molecular Morphogenesis Laboratory of Molecular Embryology National Institute of Child Health and Human Development National Institute of Health Building 18T Room 106 Bethesda MD 20892-5431 USA

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 NFkB 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.

关键词： HIV thyroid hormone receptor Histone acetylation transcriptional repression Xenopus oocyte.

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