Dissecting super-enhancer hierarchy based on chromatin interactions

Jialiang Huang, Kailong Li, Wenqing Cai, Xin Liu, Yuannyu Zhang, Stuart H. Orkin, Jian Xu () and Guo-Cheng Yuan ()
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Jialiang Huang: Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health
Kailong Li: University of Texas Southwestern Medical Center
Wenqing Cai: Harvard Medical School
Xin Liu: University of Texas Southwestern Medical Center
Yuannyu Zhang: University of Texas Southwestern Medical Center
Stuart H. Orkin: Harvard Medical School
Jian Xu: University of Texas Southwestern Medical Center
Guo-Cheng Yuan: Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-03279-9

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