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Acidic domains differentially read histone H3 lysine 4 methylation status and are widely present in chromatin-associated proteins

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Science China(Life Sciences) 2017年第2期60卷 138-151页

作者： Meng Wu Wei Wei Jiwei Chen Rong Cong Tieliu Shi Jiwen Li jiemin wong James X.Du Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Collaborative Innovation Center for Cancer Medicine Sun Yat-Sen University Cancer CenterGuangzhou 510060China University de Lyon Ecole Normale Supdrieure de LyonCNRS USR 3010Laboratoire Joliot-CurieLyon 69364France

Histone methylation is believed to provide binding sites for specific reader proteins, which translate histone code into biological function. Here we show that a family of acidic domain-containing proteins including nucleophosmin （NPM 1）, pp32, SET/TAF 113, nucleolin （NCL） and upstream binding factor （UBF） are novel H3K4me2-binding proteins. These proteins exhibit a unique pattern of interaction with methylated H3K4, as their binding is stimulated by H3K4me2 and inhibited by H3K4mel and H3K4me3. These proteins contain one or more acidic domains consisting mainly of aspartic and/or glutamic residues that are necessary for preferential binding of H3K4me2. Furthermore, we demonstrate that the acidic domain with sufficient length alone is capable of binding H3K4me2 in vitro and in vivo. NPM1, NCL and UBF require their acidic domains for association with and transcriptional activation ofrDNA genes. Interestingly, by defining acidic domain as a sequence with at least 20 acidic residues in 50 continuous amino acids, we identified 655 acidic domain-containing protein coding genes in the human genome and Gene Ontology （GO） analysis showed that many of the acidic domain proteins have chromatin-related functions. Our data suggest that acidic domain is a novel histone binding motif that can differentially read the status of H3K4 methylation and is broadly present in chromatin-associated proteins.

关键词： histone methylation H3K4mel H3K4me2 H3K4me3 acidic domain histone code transcription chromatin

MYC promotes global transcription in part by controlling P-TEFb complex formation via DNA-binding independent inhibition of CDK9 SUMOylation

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Science China(Life Sciences) 2023年第9期66卷 2167-2184页

作者： Qingqing Guan Zhaosu Chen Fang Yu Lingling Liu Yuanyong Huang Gang Wei Cheng-Ming Chiang jiemin wong Jiwen Li Shanghai Key Laboratory of Regulatory Biology Fengxian District Central Hospital-ECNU Joint Center of Translational MedicineInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Medicine UF Health Cancer CenterUniversity of FloridaGainesvilleFL 32610USA CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Simmons Comprehensive Cancer Center Department of Pharmacologyand Department of BiochemistryUniversity of Texas Southwestern Medical CenterDallas TX 75390USA

MYC is an oncogenic transcription factor with a novel role in enhancing global transcription when overexpressed. However, how MYC promotes global transcription remains controversial. Here, we used a series of MYC mutants to dissect the molecular basis for MYC-driven global transcription. We found that MYC mutants deficient in DNA binding or known transcriptional activation activities can still promote global transcription and enhance serine 2 phosphorylation(Ser2P) of the RNA polymerase(Pol) II Cterminal domain(CTD), a hallmark of active elongating RNA Pol II. Two distinct regions within MYC can promote global transcription and Ser2P of Pol II CTD. The ability of various MYC mutants to promote global transcription and Ser2P correlates with their ability to suppress CDK9 SUMOylation and enhance positive transcription elongation factor b(P-TEFb) complex formation. We showed that MYC suppresses CDK9 SUMOylation by inhibiting the interaction between CDK9 and SUMO enzymes including UBC9 and PIAS1. Furthermore, MYC's activity in enhancing global transcription positively contributes to its activity in promoting cell proliferation and transformation. Together, our study demonstrates that MYC promotes global transcription, at least in part, by promoting the formation of the active P-TEFb complex via a sequence-specific DNA-binding activity-independent manner.

关键词： MYC global transcription P-TEFb CDK9 SUMOylation cell transformation

Regulation of latency to lytic life cycle:multiple tricks by KSHV RTA

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Frontiers in Biology 2010年第2期5卷 97-97页

作者： jiemin wong The Institute of Biomedical Sciences and School of Life Sciences East China Normal UniversityShanghai 200241China

The herpesviruses are large enveloped DNA viruses that infect a wide spectrum hosts including human being.A key characteristic of all herpesviruses is their ability to establish life-time latency within the infected host and to periodically reactivate and enter the lytic replication to produce infectious virus *** latency the 120–300 kb double-stranded DNA genomes of these viruses are maintained as multiple copies of circular episomes within the nuclei of the host cells.

关键词： latency life maintained

Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells

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Nanog and Oct4 associate with unique transcriptional repress...

Structural Basis for Hydroxymethylcytosine Recognition by the SRADomain of UHRF2

第三届细胞结构与功能的信号基础研讨会

作者： Sung Yun Jung jiemin wong Austin J.Cooney The Institute of Biomedical Sciences College of Life SciencesEast China Normal UniversityShanghaiChina Stem Cells and Regenerative Medicine Center Baylor College of MedicineOne Baylor PlazaHoustonTexas 77030USA

Nanog and Oct4 are essential transcription factors that regulate self-renewal and pluripotency of ES ***,the mechanisms by which Nanog and Oct4 modulate ES cell fate remain *** characterization of endogenous Nanog and Oct4 protein complexes in mouse ES cells,we found that these transcription factors interact with each other and associate with proteins from multiple repression complexes,including the NuRD,Sin3A and Pml *** addition, Nanog,Oct4 and repressor proteins co-occupy Nanog-target genes in mouse ES cells, suggesting that Nanog and Oct4 together may communicate with distinct repression complexes to control gene *** our surprise,of the various core components in the NuRD complex with which Nanog and Oct4 interact,Mta1 was preferred,whereas Mbd3 and Rbbp7 were either absent or present at sub-stoichiometric *** named this unique Hdacl/2- and Mtal/2-containing complex NODE(for Nanog and Oct4 associated deacetylase).Interestingly,NODE contained histone deacetylase(HDAC) activity that seemed to be comparable to NuRD,and retained its association with Nanog and Oct4 in Mbd3-/- ES *** contrast to Mbd3 loss-of-function,knockdown of NODE subunits led to increased expression of developmentally regulated genes and ES-cell *** data collectively suggest that Nanog and Oct4 associate with unique repressor complexes on their target genes to control ES cell fate.

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Structural Basis for Hydroxymethylcytosine Recognition by th...

Regulation of Ubiquitin-like with PHD and RING Finger Domain 1(UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery

中国生物化学与分子生物学会第十一次会员代表大会暨2014年全国学术会议

作者： Na Yang Ting Zhou Jun Xiong Mingzhu Wang jiemin wong Bing Zhu Rui-Ming Xu Institute of Biophysics Chinese Academy of Sciences National Institute of Biological Sciences East China Normal University

Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins,a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine(5hmC), has been implicated in embryogenesis, cell differentiation,and human diseases. Recently, the SRA domain of UHRF2(UHRF2-SRA) has been reportedto specifically recognize 5hmC, but how UHRF2 recognizes this modification is *** we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. Thestructure reveals that the conformation of a phenylalanine allows the formation of an optimal5 hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmCand UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.

关键词： DNA hydroxymethylation SRA domain 5hmC recognition Epigentic regulation

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Regulation of Ubiquitin-like with PHD and RING Finger Domain...

中国生物化学与分子生物学会2016年全国学术会议

作者： Guangjin Ding Peilin Chen Hui Zhang Xiaojie Huang Yi Zang Jiwen Li Jia Li jiemin wong Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life Sciences East China Normal University National Center for Drug Screening State Key Laboratory of Drug ResearchShanghai Institute of Materia Medica Chinese Academy of Sciences

As a protein critical for the maintenance of DNA methylation and cell proliferation,UHRF1 is frequently highly expressed in various human cancers and is considered as a drug target for cancer *** a high throughput screening for small molecules that induce UHRF1 protein degradation,we have identified the Hsp90 inhibitor 17-allylamino-17-

关键词： UHRF1 HSP90 HSP70 Client Protein 17-AAG(17-allylamino-17-demethoxygeldanamycin) Protein Stability E3 Ligase

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碳纳米管本征热导率的研究进展

化工新型材料 2013年第11期41卷 1-3,16页

作者：陈强黄永华翁捷敏王如竹上海交通大学制冷与低温工程研究所上海200240

碳纳米管作为极具潜力的新型热控材料,其本征热导率是最重要的热物性参数,得到了广泛研究。总结了近二十多年来在碳纳米管本征热导率方面的研究成果,归纳为实验测量和理论方法两大类,并按基于应用的统一定义,将不同研究者的结果纳入到... 详细信息

碳纳米管作为极具潜力的新型热控材料,其本征热导率是最重要的热物性参数,得到了广泛研究。总结了近二十多年来在碳纳米管本征热导率方面的研究成果,归纳为实验测量和理论方法两大类,并按基于应用的统一定义,将不同研究者的结果纳入到同一框架下进行了比较。

关键词：碳纳米管热导率实验测量分子动力学模拟

Erratum to: Acidic domains differentially read histone H3 lysine 4methylation status and are widely present in chromatin-associated proteins

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Science China Life Sciences 2017年第6期60卷 680-680页

作者： Meng Wu Wei Wei Jiwei Chen Rong Cong Tieliu Shi Philippe Bouvet Jiwen Li jiemin wong James X.Du Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University Université de Lyon Ecole Normale Supérieure de Lyon Université de Lyon Centre de Recherche en Cancérologie de Lyon Cancer Cell Plasticity Department Collaborative Innovation Center for Cancer Medicine Sun Yat-Sen University Cancer Center

染色质可塑性动态调控的蛋白质机器及其作用机理

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中国基础科学 2018年第1期20卷 53-57页

作者：李国红翁杰敏吴强俞洋中国科学院生物物理研究所北京100101 华东师范大学生命科学学院上海200062 上海交通大学系统生物医学研究院上海200240

后基因组时代生命科学领域的一大关键科学问题是同一生物体中具有相同基因组的各种不同生理功能的细胞命运是如何决定的。表观遗传学正是为了回答这一关键科学问题而兴起的新兴学科,而表观遗传学的核心是染色质结构与功能层面的动态调... 详细信息

后基因组时代生命科学领域的一大关键科学问题是同一生物体中具有相同基因组的各种不同生理功能的细胞命运是如何决定的。表观遗传学正是为了回答这一关键科学问题而兴起的新兴学科,而表观遗传学的核心是染色质结构与功能层面的动态调控。高等真核生物的基因组DNA通过缠绕组蛋白八聚体形成以核小体为重复单元的串珠结构,并经不同层次折叠如30 nm染色质纤维、长距离染色质环、异染色质等高级结构储存于细胞核中。现有研究表明,染色质而非孤立的DNA才是真核生物遗传信息的载体,同时也是基因转录、DNA复制与损伤修复、DNA重排和重组等生命活动赖以进行并得以精准调控的物质基础和信息整合平台。染色质结构及其功能的动态调控在生殖发育、细胞分化、代谢和衰老等过程中发挥至关重要的作用,其错误调控常导致基因表达异常并伴随多种疾病的发生。同时,国际上以染色质动态调控相关因子为靶标的药物研发方兴未艾,累计投入已超过数十亿美元,目前已有多种染色质修饰酶抑制剂被美国FDA批准成药。因此,染色质结构与功能的动态调控既是揭示生命现象本质、正确理解生命过程以及各种人类重要疾病发生发展的基础生物学问题之一,也是涉及国民健康和医药产业发展的重大战略需求。

关键词：表观遗传染色质动态调控基因转录调控