Three-dimensional interactions between enhancers and promoters during intestinal differentiation depend upon HNF4
Open accessAbstract
Cells in renewing tissues exhibit dramatic transcriptional changes as they differentiate. The contribution of chromatin looping to tissue renewal is incompletely understood. Enhancer-promoter interactions could be relatively stable as cells transition from progenitor to differentiated states; alternatively, chromatin looping could be as dynamic as the gene expression from their loci. The intestinal epithelium is the most rapidly renewing mammalian tissue. Proliferative cells in crypts of Lieberkühn sustain a stream of differentiated cells that are continually shed into the lumen. We apply chromosome conformation capture combined with chromatin immunoprecipitation (HiChIP) and sequencing to measure enhancer-promoter interactions in progenitor and differentiated cells of the intestinal epithelium. Despite dynamic gene regulation across the differentiation axis, we find that enhancer-promoter interactions are relatively stable. Functionally, we find HNF4 transcription factors are required for chromatin looping at target genes. Depletion of HNF4 disrupts local chromatin looping, histone modifications, and target gene expression. This study provides insights into transcriptional regulatory mechanisms governing homeostasis in renewing tissues.
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Using techniques with antibodies to enhancer- and promoter-associated histone modifications or RNA polymerase has revealed large numbers of 3D enhancer-promoter contacts.
“Using these techniques with antibodies to enhancer- and promoter-associated histone modifications or those to RNA polymerase has also revealed large numbers of 3D enhancer–promoter contacts [244, 295–301].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [300]
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- Authors
- Chen, L., Cao, W., Aita, R., Aldea, D., Flores, J., Gao, N., Bonder, E. M., Ellison, C. E., & Verzi, M. P.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Verzi, Michael P.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 34
- Issue
- 4
- Pages
- 108679
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC7899294
- OpenAlex
- W3123061908
- Cited by
- 27
- References
- 51
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 3
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- Rutgers Cancer Institute of New Jersey (P30CA072720)
- National Institute of Allergy and Infectious Diseases (U01 DK103141)
- National Institutes of Health (P30CA072720, R01DK121915, R01GM130698, R01CA190558)
- National Institute of Diabetes and Digestive and Kidney Diseases
- 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 › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- enhancer-promoter interactions, chromatin looping, HNF4, intestinal epithelium, intestinal differentiation, tissue renewal, histone modifications, transcriptional regulation, HiChIP
- MeSH terms
- Cell Differentiation, Chromatin, Enhancer Elements, Genetic, Humans, Intestinal Mucosa, Promoter Regions, Genetic, Hepatocyte Nuclear Factor 4
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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