Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA
Open accessAbstract
FoxA proteins are pioneer transcription factors, among the first to bind chromatin domains in development and enable gene activity. The Fox DNA-binding domain structurally resembles linker histone and binds nucleosomes stably. Using fluorescence recovery after photobleaching, we found that FoxA1 and FoxA2 move much more slowly in nuclei than other transcription factor types, including c-Myc, GATA-4, NF-1, and HMGB1. We find that slower nuclear mobility correlates with high nonspecific nucleosome binding, and point mutations that disrupt nonspecific binding markedly increase nuclear mobility. FoxA's distinct nuclear mobility is consistent with its pioneer activity in chromatin.
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FOXA TFs can bind condensed chromatin and act as placeholders or recruit factors for transcriptional initiation.
“FOXAs have a structural similarity to linker histories and are able to bind condensed chromatin, where they can either passively act as placeholders for recruitment of factors later in development or actively recruit other factors for transcriptional initiation (Sekiya et al., 2009; Zaret and Carroll, 2011).”
From Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation (2014) · cites this paper as Sekiya et al., 2009
The paper’s Abstract (page unavailable) reports that FoxA can bind highly compacted nucleosome arrays and occupy a target site while the gene remains silent. “Nuclear mobility and pioneer factor function” (page unavailable) suggests that stable FoxA binding allows other factors to engage chromatin, but it does not establish that FoxA actively recruits them for transcriptional initiation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFOXA2 is a well-established pioneer factor.
“FOXA2 is a wellestablished pioneer factor (Sekiya et al. 2009), while HNF4A and PDX1 are not.”
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 Sekiya et al. 2009
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Cites
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“Second, FoxA1 and FoxA2 factors are highly conserved in metazoan endoderm development (Davidson and Erwin 2006) and are redundantly necessary in the endoderm for alb1 induction and liver development (Lee et al.”
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Bossard, P., & Zaret, K. S. (1998) · Development · doi:10.1242/dev.125.24.4909 · Cited by 313 · see citing works
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Pioneer transcription factors: establishing competence for gene expression
Zaret, K. S., & Carroll, J. S. (2011) · Genes & Development · doi:10.1101/gad.176826.111 · Cited by 1,589 · see citing works
Self-citationDistinct structural classes of activating FOXA1 alterations in advanced prostate cancer
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“FOXA2 is a wellestablished pioneer factor (Sekiya et al. 2009), while HNF4A and PDX1 are not.”
BackgroundInfluentialHippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation
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“FOXAs have a structural similarity to linker histories and are able to bind condensed chromatin, where they can either passively act as placeholders for recruitment of factors later in development or actively recruit other factors for transcriptional initiation (Sekiya et al., 2009; Zaret and Carroll, 2011).”
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The mechanistic basis for chromatin regulation by pioneer transcription factors
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Chromatin scanning by dynamic binding of pioneer factors
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Self-citation
- Authors
- Sekiya, T., Muthurajan, U. M., Luger, K., Tulin, A. V., & Zaret, K. S.
- Affiliations
- Fox Chase Cancer Center (US)
- Colorado State University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-04-01
- Volume
- 23
- Issue
- 7
- Pages
- 804-809
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2666343
- OpenAlex
- W2099848965
- Cited by
- 221
- References
- 3
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 12 · 2023: 15 · 2022: 13 · 2021: 9 · 2020: 12 · 2019: 15 · 2018: 19 · 2017: 16 · 2016: 14 · 2015: 13 · 2014: 14 · 2013: 17 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- National Institutes of Health (R37GM36477)
- Fox Chase Cancer Center
- Japan Society for the Promotion of Science
- National Institute of General Medical Sciences (R01GM061909, GM077452, GM061909, R37GM036477, R01/R37GM36477, R01GM077452)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- FoxA, pioneer transcription factors, nuclear mobility, nucleosome binding, nonspecific DNA binding, FOXA1, FOXA2, chromatin accessibility
- MeSH terms
- Animals, Cell Line, Cell Nucleus, Mutation, Nucleosomes, Protein Binding, Transcription Factors, Protein Transport, Mice, Hepatocyte Nuclear Factor 3-alpha, Hepatocyte Nuclear Factor 3-beta
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