FoxA1 Translates Epigenetic Signatures into Enhancer-Driven Lineage-Specific Transcription
Open accessAbstract
Complex organisms require tissue-specific transcriptional programs, yet little is known about how these are established. The transcription factor FoxA1 is thought to contribute to gene regulation through its ability to act as a pioneer factor binding to nucleosomal DNA. Through genome-wide positional analyses, we demonstrate that FoxA1 cell type-specific functions rely primarily on differential recruitment to chromatin predominantly at distant enhancers rather than proximal promoters. This differential recruitment leads to cell type-specific changes in chromatin structure and functional collaboration with lineage-specific transcription factors. Despite the ability of FoxA1 to bind nucleosomes, its differential binding to chromatin sites is dependent on the distribution of histone H3 lysine 4 dimethylation. Together, our results suggest that methylation of histone H3 lysine 4 is part of the epigenetic signature that defines lineage-specific FoxA1 recruitment sites in chromatin. FoxA1 translates this epigenetic signature into changes in chromatin structure thereby establishing lineage-specific transcriptional enhancers and programs.
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Low H3K4me1 loci are typically functionally inactive and not co-occupied.
“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 Lupien et al. 2008
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- Authors
- Lupien, M., Eeckhoute, J., Meyer, C. A., Wang, Q., Zhang, Y., Li, W., Carroll, J. S., Liu, X. S., & Brown, M.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Corresponding author
- Brown, Myles
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 132
- Issue
- 6
- Pages
- 958-970
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2323438
- OpenAlex
- W2166037178
- Cited by
- 983
- References
- 4
- Citations by year
- 2026: 30 · 2025: 25 · 2024: 37 · 2023: 48 · 2022: 42 · 2021: 41 · 2020: 35 · 2019: 49 · 2018: 40 · 2017: 52 · 2016: 57 · 2015: 43 · 2014: 67 · 2013: 88 · 2012: 88
- FWCI
- 32.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Human Genome Research Institute (R01HG004069)
- National Cancer Institute (P01CA8011105, P01CA080111, P50CA089393)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074967, R56DK074967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- FOXA1, pioneer transcription factors, enhancers, chromatin structure, nucleosome binding, epigenetic signatures, transcription factor recruitment, cell type-specific gene regulation
- MeSH terms
- Enhancer Elements, Genetic, Estrogens, Histones, Humans, Methylation, Receptors, Androgen, Transcription, Genetic, Genome, Human, Chromatin Assembly and Disassembly, Histone Code, Epigenesis, Genetic, Cell Line, Tumor, Chromatin Immunoprecipitation, Estrogen Receptor alpha, Hepatocyte Nuclear Factor 3-alpha
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