Huang Jialiang, Li Kailong, Cai Wenqing, Liu Xin, Zhang Yuannyu, Orkin Stuart H, Xu Jian, Yuan Guo-Cheng
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA.
Division of Hematology/Oncology, Boston Childrens Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.
Nat Commun. 2018 Mar 5;9(1):943. doi: 10.1038/s41467-018-03279-9.
Recent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape. As such, hub enhancers are the major constituents responsible for SE functional and structural organization.
近期研究强调了超级增强子（SEs）作为基因表达重要调控元件的作用，但其内在特性仍未完全明确。通过对Hi-C和ChIP-seq数据的综合分析，我们发现相当一部分SEs呈层级组织，包含中心增强子和非中心增强子。中心增强子与非中心增强子具有相似的组蛋白标记，但与黏连蛋白和CTCF结合位点以及疾病相关遗传变异有明显关联。中心增强子的基因敲除会导致基因激活和局部染色质景观出现严重缺陷。因此，中心增强子是SE功能和结构组织的主要组成部分。
