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Dissecting super-enhancer hierarchy based on chromatin interactions
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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.
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“Review of diverse, albeit incomplete, previous analyses of SEs16,17,19,20,22 suggest that facilitators, as described here, may be relatively common elements in multipartite enhancers.”
From Super-enhancers include classical enhancers and facilitators to fully activate gene expression (2023) · cites this paper as [20]
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“When comparing Borzoi, Enformer and a distance-to-TSS baseline on their ability to classify measured positive from negative enhancer–gene interactions in data from previous works60–65, we find that Borzoi has superior average precision (AUPRC) and area under the receiver operating characteristic curve (AUROC) at all distances (Fig. 4c and Extended Data Fig. 5a).”
From Predicting RNA-seq coverage from DNA sequence as a unifying model of gene regulation (2025) · cites this paper as [64]
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Metadata
- Authors
- Huang, J., Li, K., Cai, W., Liu, X., Zhang, Y., Orkin, S. H., Xu, J., & Yuan, G.-C.
- Affiliations
- Boston Children's Hospital (US)
- Children's Medical Center (US)
- Harvard University (US)
- Corresponding author
- Xu, Jian
- Yuan, Guo-Cheng
- Venue
- Nature Communications
- Published
- 2018-03-05
- Volume
- 9
- Issue
- 1
- Pages
- 943-943
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5838163
- OpenAlex
- W2952336494
- Cited by
- 241
- References
- 74
- Citations by year
- 2026: 22 · 2025: 20 · 2024: 22 · 2023: 27 · 2022: 37 · 2021: 43 · 2020: 30 · 2019: 25 · 2018: 14
- FWCI
- 11.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Cancer Society (IRG‐02‐196, 02-196)
- Cancer Prevention and Research Institute of Texas (RR140025)
- University of Texas Southwestern Medical Center
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL119099)
- National Human Genome Research Institute (R01HG009663)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK093543, R03DK101665, R01DK111430)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- super-enhancers, chromatin interactions, cohesin, CTCF binding sites, histone modifications, disease-associated variants, gene activation, chromatin landscape
- MeSH terms
- Gene Editing, CCCTC-Binding Factor, Cohesins, Chromatin, Chromosomal Proteins, Non-Histone, Disease, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Models, Genetic, Protein Binding, Genetic Variation, Cell Cycle Proteins, K562 Cells, Gene Knockout Techniques, Human Umbilical Vein Endothelial Cells, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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