Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.
Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.
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DOI：
10.1101/gr.201038.115
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发表时间：
2016-05
期刊：
影响因子：
7
通讯作者：
Prabhakar S
中科院分区：
文献类型：
--
作者：
Kumar V;Rayan NA;Muratani M;Lim S;Elanggovan B;Xin L;Lu T;Makhija H;Poschmann J;Lufkin T;Ng HH;Prabhakar S
尽管已经描述了超过 35 种不同的组蛋白乙酰化标记，但绝大多数调控基因组学研究仅集中于 H3K27ac 和 H3K9ac。为了鉴定调控元件的新表观基因组特征，我们通过在人类 T 细胞中进行 140 次增强子测定，构建了一组经过验证的增强子基准。我们在这个无偏增强子集上测试了 40 个染色质特征，并确定 H2BK20ac（一种很少被研究的组蛋白修饰）作为活性增强子最具预测性的标记。值得注意的是，我们检测到一类功能独特的新型增强子，富含 H2BK20ac，但缺乏 H3K27ac，这种增强子存在于所有检查的细胞系以及胚胎前脑组织中。 H2BK20ac 在突出细胞类型特异性启动子方面也很独特。相反，无论细胞类型特异性如何，所有活性启动子中都存在其他乙酰化标记。在受刺激的小胶质细胞中，H2BK20ac 比 H3K27ac 与细胞状态特异性表达变化更相关，TGF-β 信号传导可解耦调节元件子集的两个乙酰化标记。总之，我们的研究揭示了组蛋白乙酰化与细胞类型特异性基因调控之间以前未知的联系，并表明 H2BK20ac 分析可用于揭示基因调控的新维度。
Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation.