Histone Crotonylation: Enzymes and Function in Transcription and beyond
發布時間 :2018-12-10  閱讀次數 :6129

報告人👲🏿:翁傑敏

單  位:華東師範大學生命科學EON4

時  間:2018.12.12(周三) 15:00-16:00

地  點:生物藥學樓#2-116

報告30分鐘,交流15-20分鐘

聯系人:張曉蕾

聯系方式:18321362165

 

報告摘要:

Recent studies indicate that, in addition to acetylation, lysine residues in histones are subjected to various types of acylation including malonylation, propionylation, crotonylation and etc, raising the question as to the functions and enzymes for different types of histone acylation. As crotonylation occurs broadly in core histones and has been implicated in transcriptional regulation, we focus our attention on enzymes catalyzing dynamic histone crotonylation. We demonstrate that among the known histone acetyltransferases (HAT), only CBP/p300 and MOF possess histone crotonyltransferase (HCT) activity. We show that CBP and p300 are likely the major HCTs in mammalian cells, whereas MOF is an evolutionarily conserved HCT. By generating novel CBP/p300 mutants with deficient HAT but competent HCT activity, we demonstrated that CBP/p300 can stimulate transcriptional activation in the absence of HAT activity. We also present evidence that class I histone deacetylases (HDACs) rather than sirtuin family deacetylases (SIRTs) are the major histone decrotonylases (HDCRs) and that histone crotonylation is as dynamic as histone acetylation in mammalian cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired HDAC but sustained HDCR activity. Using these mutants we demonstrate that selective histone decrotonylation in mammalian cells correlates with a broad transcriptional repression. Together our studies provide compelling evidence that in transcriptional regulation histone crotonylation plays a broad and no-redundant function to acetylation. Furthermore, we will present evidence that crotonylation is a potential biomarker for cancer diagnosis and that aberrant histone propionylation is associated with type II diabetes.

 

 

報告人簡介🩸👩🏿‍🎓:

翁傑敏教授,2007至今任華東師範大學生命科學EON4特聘教授🏮、生命醫學研究所副所長。長期從事表觀遺傳調控和細胞核激素受體研究🧗‍♂️,在表觀遺傳調控和細胞核激素受體轉錄調控領域做出了較出色的研究工作,分別榮獲了2001年美國內分泌協會優秀青年科學家獎和Baylor 醫EON4細胞與分子生物學系2005優秀科研獎。已在國外核心期刊🙇🏿‍♂️,包括 Cell,Nature,Science, Mol. Cell,Cell Res., Nat. Commun., EMBO J. 和MCB 等重要國際學術刊物發表論文100余篇,文章引用9000多次,2014-2017年入選高被引中國學者榜單。主要學術兼職有中國遺傳學會表觀遺傳分會副主任🎪☝️,中國細胞生物學會染色質生物學分會副主任。

 

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