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Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers
Open accessAbstract
Selective activity of a specific set of enhancers defines tissue-specific gene transcription. The pioneer factor FOXA1 has been shown to induce functional enhancer competency through chromatin openings. We have previously found that FOXA1 is recruited to thousands of regions across the genome of a given cell type. Here, we monitored the chromatin structure at FOXA1 binding sites on a chromosome-wide scale using formaldehyde assisted isolation of regulatory elements (FAIRE). Surprisingly, we find that a significant fraction of FOXA1-bound sites have a relatively closed chromatin conformation linked to a shift of the epigenetic signature toward repressive histone marks. Importantly, these sites are not correlated with gene expression in a given cell type suggesting that FOXA1 is required, but not sufficient, for the functional activity of bound enhancers. Interestingly, we find that a significant proportion of the inactive FOXA1-bound regulatory sites in one cell type are actually functional in another cellular context. We found that at least half of the FOXA1 binding sites from a given cell type are shared with another cell lineage. Mechanisms that restrict the activity of shared FOXA1-bound enhancers likely play a significant role in defining the cell-type-specific functions of FOXA1.
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“In support of this, our data show that these loci are typically functionally inactive and not co-occupied, in agreement with previous studies (Lupien et al. 2008;Eeckhoute et al. 2009).”
From Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver (2010) · cites this paper as Eeckhoute et al. 2009
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Metadata
- Authors
- Eeckhoute, J., Lupien, M., Meyer, C. A., Verzi, M. P., Shivdasani, R. A., Liu, X. S., & Brown, M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-01-07
- Volume
- 19
- Issue
- 3
- Pages
- 372-380
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC2661808
- OpenAlex
- W2147789776
- Cited by
- 106
- References
- 63
- Citations by year
- 2026: 1 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 16
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Funders
- Dana-Farber Cancer Institute
- Dana-Farber/Harvard Cancer Center
- Centre National de la Recherche Scientifique
- National Human Genome Research Institute (R01HG004069)
- National Cancer Institute (P01CA8011105)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074967)
- 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
- FOXA1, enhancers, chromatin remodeling, cell type specificity, FAIRE, chromatin accessibility, histone modifications, pioneer factors
- MeSH terms
- Binding Sites, Chromosome Mapping, Enhancer Elements, Genetic, Humans, Organ Specificity, Protein Binding, Tumor Cells, Cultured, Transcriptional Activation, Conserved Sequence, Cell Lineage, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Chromatin Assembly and Disassembly, Hepatocyte Nuclear Factor 3-alpha
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