Dissecting super-enhancer hierarchy based on chromatin interactions

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...

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Bibliographic Details
Published in:Nature communications 2018-03, Vol.9 (1), p.943-12, Article 943
Main Authors: Huang, Jialiang, Li, Kailong, Cai, Wenqing, Liu, Xin, Zhang, Yuannyu, Orkin, Stuart H., Xu, Jian, Yuan, Guo-Cheng
Format: Article
Language:English
Subjects:
38/15
38/23
38/39
38/77
42/70
631/114/2114
631/208/177
631/337/100/101
631/337/572
Binding sites
CCCTC-Binding Factor - metabolism
Cell Cycle Proteins - metabolism
Chromatin
Chromatin - metabolism
Chromosomal Proteins, Non-Histone - metabolism
Cohesin
Cohesins
CRISPR-Cas Systems - genetics
Disease - genetics
Enhancer Elements, Genetic
Enhancers
Functional morphology
Gene Editing
Gene expression
Gene Expression Regulation
Gene Knockout Techniques
Genetic diversity
Genetic variance
Genetic Variation
Human Umbilical Vein Endothelial Cells - metabolism
Humanities and Social Sciences
Humans
K562 Cells
Models, Genetic
multidisciplinary
Protein Binding
Regulatory sequences
Science
Science (multidisciplinary)
Structure-function relationships
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Description
Summary: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. Super-enhancers (SEs) are important regulatory elements for gene expression, but their intrinsic properties remain poorly understood. Here the authors analyse Hi-C and ChIP-seq data and find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-03279-9