East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China.
East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China.
East China Normal Univ, Joint Res Ctr Translat Med, 6600 Nanfeng Rd, Shanghai 201499, Peoples R China.
Shanghai Fengxian Dist Cent Hosp, 6600 Nanfeng Rd, Shanghai 201499, Peoples R China.
China Agr Univ, Beijing Adv Innovat Ctr Food Nutr & Human Hlth, Beijing 100193, Peoples R China.
Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Urol, 600 Yishan Rd, Shanghai 200233, Peoples R China.
Shanghai Sixth Peoples Hosp, Dept Urol, South Campus,6600 Nanfeng Rd, Shanghai 201499, Peoples R China.
Recent studies on enzymes and reader proteins for histone crotonylation support a function of histone crotonylation in transcription. However, the enzyme(s) responsible for histone decrotonylation (HDCR) remains poorly defined. 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 crotonylation is as dynamic as histone 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 crotonylation but not acetylation reader proteins. Furthermore, we show that histone crotonylation is enriched in and required for self-renewal of mouse embryonic stem cells.收起