Pradeepa Madapura M, Grimes Graeme R, Kumar Yatendra, Olley Gabrielle, Taylor Gillian C A, Schneider Robert, Bickmore Wendy A
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK.
School of Biological Sciences, University of Essex, Colchester, UK.
Nat Genet. 2016 Jun;48(6):681-6. doi: 10.1038/ng.3550. Epub 2016 Apr 18.
Histone acetylation is generally associated with active chromatin, but most studies have focused on the acetylation of histone tails. Various histone H3 and H4 tail acetylations mark the promoters of active genes. These modifications include acetylation of histone H3 at lysine 27 (H3K27ac), which blocks Polycomb-mediated trimethylation of H3K27 (H3K27me3). H3K27ac is also widely used to identify active enhancers, and the assumption has been that profiling H3K27ac is a comprehensive way of cataloguing the set of active enhancers in mammalian cell types. Here we show that acetylation of lysine residues in the globular domain of histone H3 (lysine 64 (H3K64ac) and lysine 122 (H3K122ac)) marks active gene promoters and also a subset of active enhancers. Moreover, we find a new class of active functional enhancers that is marked by H3K122ac but lacks H3K27ac. This work suggests that, to identify enhancers, a more comprehensive analysis of histone acetylation is required than has previously been considered.
组蛋白乙酰化通常与活性染色质相关，但大多数研究都集中在组蛋白尾巴的乙酰化上。各种组蛋白H3和H4尾巴乙酰化标记了活性基因的启动子。这些修饰包括组蛋白H3赖氨酸27位点的乙酰化（H3K27ac），它会阻断多梳蛋白介导的H3K27三甲基化（H3K27me3）。H3K27ac也被广泛用于识别活性增强子，并且一直以来的假设是，分析H3K27ac是对哺乳动物细胞类型中活性增强子集合进行编目的一种全面方法。在此我们表明，组蛋白H3球状结构域中的赖氨酸残基乙酰化（赖氨酸64位点（H3K64ac）和赖氨酸122位点（H3K122ac））标记了活性基因启动子以及一部分活性增强子。此外，我们发现了一类新的活性功能增强子，其以H3K122ac标记但缺乏H3K27ac。这项工作表明，为了识别增强子，需要对组蛋白乙酰化进行比以往所认为的更全面的分析。
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