Histone Crotonylation: Enzymes and Function in Transcription and beyond

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单  位:华东师范大学生命科学学院

时  间:2018.12.12(周三) 15:00-16:00

地  点:生物药学楼#2-116






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.




翁杰敏教授,2007至今任华东师范大学生命科学学院特聘教授、生命医学研究所副所长。长期从事表观遗传调控和细胞核激素受体研究,在表观遗传调控和细胞核激素受体转录调控领域做出了较出色的研究工作,分别荣获了2001年美国内分泌协会优秀青年科学家奖和Baylor 医学院细胞与分子生物学系2005优秀科研奖。已在国外核心期刊,包括 Cell,Nature,Science, Mol. Cell,Cell Res., Nat. Commun., EMBO J. 和MCB 等重要国际学术刊物发表论文100余篇,文章引用9000多次,2014-2017年入选高被引中国学者榜单。主要学术兼职有中国遗传学会表观遗传分会副主任,中国细胞生物学会染色质生物学分会副主任。


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