小柯机器人

丹麦哥本哈根大学Chunaram Choudhary近期取得重要工作进展，他们研究利用组蛋白H2B的乙酰化来标记活性增强子并预测CBP/p300靶基因。相关研究成果2023年4月6日在线发表于《自然—遗传学》杂志上。

据介绍，染色质特征被广泛用于增强子的基因组规模映射。然而，将活性增强子与其他顺式调节元件区分开来，预测增强子强度并鉴定其靶标基因是具有挑战性的。

研究人员建立了组蛋白H2B N-末端多位点赖氨酸乙酰化（H2BNTac）作为活性增强子的标志。H2BNTac显著标记候选活性增强子和启动子子集，并将其与普遍存在的活性启动子区分开来。H2BNTac的特异性有两种机制：（1）与H3K27ac不同，H2BNTak是由CBP/p300特异性催化的；（2） H2A–H2B，而不是H3–H4，通过转录诱导的核小体重塑快速交换。H2BNTac阳性候选增强子在正交增强子活性测定中显示出高的验证率，并且绝大多数内源性活性增强子以H2BNTak和H3K27ac为标记。值得注意的是，H2BNTac强度预测增强子强度，并且在预测CBP/p300靶基因方面优于当前最先进的模型。

总之，这些发现对生成详细的增强子图谱和建模CBP/p300依赖的基因调控具有广泛的意义。

附：英文原文

Title: Acetylation of histone H2B marks active enhancers and predicts CBP/p300 target genes

Author: Narita, Takeo, Higashijima, Yoshiki, Kilic, Sinan, Liebner, Tim, Walter, Jonas, Choudhary, Chunaram

Issue&Volume: 2023-04-06

Abstract: Chromatin features are widely used for genome-scale mapping of enhancers. However, discriminating active enhancers from other cis-regulatory elements, predicting enhancer strength and identifying their target genes is challenging. Here we establish histone H2B N-terminus multisite lysine acetylation (H2BNTac) as a signature of active enhancers. H2BNTac prominently marks candidate active enhancers and a subset of promoters and discriminates them from ubiquitously active promoters. Two mechanisms underlie the distinct H2BNTac specificity: (1) unlike H3K27ac, H2BNTac is specifically catalyzed by CBP/p300; (2) H2A–H2B, but not H3–H4, are rapidly exchanged through transcription-induced nucleosome remodeling. H2BNTac-positive candidate enhancers show a high validation rate in orthogonal enhancer activity assays and a vast majority of endogenously active enhancers are marked by H2BNTac and H3K27ac. Notably, H2BNTac intensity predicts enhancer strength and outperforms current state-of-the-art models in predicting CBP/p300 target genes. These findings have broad implications for generating fine-grained enhancer maps and modeling CBP/p300-dependent gene regulation.

DOI: 10.1038/s41588-023-01348-4

Source: https://www.nature.com/articles/s41588-023-01348-4

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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