Class I histone deacetylases are major histone decrotonylases： evidence for critical and broad function of histone crotonylation in transcription  

作　　者：Wei Wei Xiaoguang Liu Jiwei Chen Shennan Gao Lu Lu Huifang Zhang Guangjin Ding Zhiqiang Wang Zhongzhou Chen Tieliu Shi Jiwen Li Jianjun Yu Jiemin Wong 

机构地区：[1]Shanghai Key Laboratory of Regulatory Biology, The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China [2]Joint Research Center for Translational Medicine, East China Normal University and Shanghai Fengxian District Central Hospital, No. 6600, Nanfeng Road, New Nanqiao Town, Fengxian District, Shanghai 201499, China [3]Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100193, China [4]Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Xuhui District, Shanghai 200233, China [5]Department of Urology, Shanghai Sixth People's Hospital South Campus, No. 6600, Nanfeng Road, New Nanqiao Town, Fengxian District, Shanghai 201499, China

出　　处：《Cell Research》2017年第7期898-915,共18页细胞研究（英文版）

基　　金：We thank members of Wong＇s laboratory for valuable discussion.We thank Dr Cheng-Ming Chiang （UT Southwestern） for critical reading of the manuscript. This study is supported by grants from the National Science and Technology Major Project ＂Key New Drug Creation and Manufacturing Program＂ of China （2014ZX09507002- 005 to JW）, the Ministry of Science and Technology of China （2015CB910402 to JW）, the National Natural Science Foundation of China （81530078 and 31571325 to JW）, the Science and Tech- nology Commission of Shanghai Municipality （14XD1401700 and 11DZ2260300 to JW）.

摘　　要：Recent studies on enzymes and reader proteins for histone crotonylation support a function of histone crotonyla- tion in transcription. However, the enzyme（s） responsible for histone decrotonylation （HDCR） remains poorly de- fined. Moreover, it remains to be determined if histone crotonylation is physiologically significant and functionally distinct from or redundant to histone acetylation. Here we present evidence that class I histone deacetylases （HDACs） rather than sirtuin family deacetylases （SIRTs） are the major histone decrotonylases, and that histone erotonylation is as dynamic as bistone acetylation in mammalian cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired HDAC but intact HDCR activity. Using these mutants we demonstrate that selective HDCR in mammalian cells correlates with a broad transcriptional repression and diminished promoter association of cro- tonylation but not acetylation reader proteins. Furthermore, we show that histone erotonylation is enriched in and required for self-renewal of mouse embryonic stem cells.

关 键 词：class I histone deacetylases histone decrotonylation histone deacetylation histone deacylation HDAC SIRT 

分 类 号：Q[生物学]