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

Wei Wei, Xiaoguang Liu, Jiwei Chen, Shennan Gao, Lu Lu, Huifang Zhang, Guangjin Ding, Zhiqiang Wang, Zhongzhou Chen, Tieliu Shi, Jiwen Li, Jianjun Yu (+1 others)
2017 Cell Research  
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
more » ... RTs) 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.
doi:10.1038/cr.2017.68 pmid:28497810 pmcid:PMC5518989 fatcat:t5ubjlqnzrbmbmr45uvqb3rc6i