组蛋白H3
生物
乙酰化
增强子
组蛋白
SAP30型
细胞生物学
组蛋白乙酰转移酶
组蛋白密码
异染色质蛋白1
EZH2型
组蛋白H2A
转录因子
遗传学
异染色质
基因
核小体
染色质
作者
Sara Martire,Aishwarya A. Gogate,Amanda Whitmill,Amanuel Tafessu,Jennifer Nguyen,Yu‐Ching Teng,Melodi Tastemel,Laura A. Banaszynski
出处
期刊:Nature Genetics
[Springer Nature]
日期:2019-05-31
卷期号:51 (6): 941-946
被引量:124
标识
DOI:10.1038/s41588-019-0428-5
摘要
The histone variant H3.3 is enriched at enhancers and active genes, as well as repeat regions such as telomeres and retroelements, in mouse embryonic stem cells (mESCs)1–3. Although recent studies demonstrate a role for H3.3 and its chaperones in establishing heterochromatin at repeat regions4–8, the function of H3.3 in transcription regulation has been less clear9–16. Here, we find that H3.3-specific phosphorylation17–19 stimulates activity of the acetyltransferase p300 in trans, suggesting that H3.3 acts as a nucleosomal cofactor for p300. Depletion of H3.3 from mESCs reduces acetylation on histone H3 at lysine 27 (H3K27ac) at enhancers. Compared with wild-type cells, those lacking H3.3 demonstrate reduced capacity to acetylate enhancers that are activated upon differentiation, along with reduced ability to reprogram cell fate. Our study demonstrates that a single amino acid in a histone variant can integrate signaling information and impact genome regulation globally, which may help to better understand how mutations in these proteins contribute to human cancers20,21. Phosphorylation of histone H3.3 at serine 31 by CHK1 is shown to stimulate activity of the acetyltransferase p300 in trans. Depletion of histone H3.3 in embryonic stem cells reduces enhancer acetylation during differentiation.
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