Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function
Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function
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高乙酰化的染色质结构域标志着细胞类型特异性基因，并提示增强子功能的不同模式
DOI：
10.1038/s41467-020-18303-0
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发表时间：
2020-09-11
影响因子：
16.6
通讯作者：
Bulger, Michael
中科院分区：
文献类型：
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作者：
Fox, Sierra;Myers, Jacquelyn A.;Bulger, Michael
在ChIP-seq测定中，通过信号强度对增强子进行分层，已经建立了超级增强子，作为鉴定细胞类型特异性、高表达基因和相关途径的广泛而有用的工具。我们研究了一种独特的分层方法，侧重于峰宽，称为超乙酰化染色质结构域（HCDs），它分类广泛的区域表现出与基因激活相关的组蛋白修饰。我们发现，这种分析有助于识别比使用多个数据集的超级增强子分析更高表达和更接近细胞身份的基因。此外，选定的基因位点的遗传操作表明，一些增强子位于HCD的工作至少部分通过一个独特的机制，涉及跨域组蛋白修饰的调制，这种活性可以导入到异源基因位点。此外，这样的遗传解剖揭示了超增强概念可以掩盖组成元素的重要功能。
Stratification of enhancers by signal strength in ChIP-seq assays has resulted in the establishment of super-enhancers as a widespread and useful tool for identifying cell type-specific, highly expressed genes and associated pathways. We examine a distinct method of stratification that focuses on peak breadth, termed hyperacetylated chromatin domains (HCDs), which classifies broad regions exhibiting histone modifications associated with gene activation. We find that this analysis serves to identify genes that are both more highly expressed and more closely aligned to cell identity than super-enhancer analysis does using multiple data sets. Moreover, genetic manipulations of selected gene loci suggest that some enhancers located within HCDs work at least in part via a distinct mechanism involving the modulation of histone modifications across domains and that this activity can be imported into a heterologous gene locus. In addition, such genetic dissection reveals that the superenhancer concept can obscure important functions of constituent elements.