Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing
Open accessAbstract
Gene expression is regulated by combinations of transcription factors, which can be mapped to regulatory elements on a genome-wide scale using ChIP experiments. In a previous ChIP-chip study of USF1 and USF2 we found evidence also of binding of GABP, FOXA2 and HNF4a within the enriched regions. Here, we have applied ChIP-seq for these transcription factors and identified 3064 peaks of enrichment for GABP, 7266 for FOXA2 and 18783 for HNF4a. Distal elements with USF2 signal was frequently bound also by HNF4a and FOXA2. GABP peaks were found at transcription start sites, whereas 94% of FOXA2 and 90% of HNF4a peaks were located at other positions. We developed a method to accurately define TFBS within peaks, and found the predicted sites to have an elevated conservation level compared to peak centers; however the majority of bindings were not evolutionary conserved. An interaction between HNF4a and GABP was seen at TSS, with one-third of the HNF4a positive promoters being bound also by GABP, and this interaction was verified by co-immunoprecipitations.
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HNF4A cooperates with the FOXA family and GATA6 of pioneer factors.
“HNF4A is known to cooperate with the FOXA family and GATA6 of pioneer factors12,49,55.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [55]
The Results section ('Co-identified motifs in peaks correspond to in vivo binding'; page not available) says FOXA2 is known to bind with HNF4a and reports FOXA motifs near HNF4a sites. The Introduction identifies FOXA2 as a pioneering factor. These passages support cooperation with FOXA2, but the copy does not establish cooperation with the FOXA family generally or with GATA6 (searched: GATA6). (LLM, conf=0.86)
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Cites
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- Authors
- Wallerman, O., Motallebipour, M., Enroth, S., Patra, K., Bysani, M. S. R., Komorowski, J., & Wadelius, C.
- Affiliations
- Uppsala University (SE)
- Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw (PL)
- Corresponding author
- Wadelius, Claes
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-10-10
- Volume
- 37
- Issue
- 22
- Pages
- 7498-7508
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2794179
- OpenAlex
- W2083266173
- Cited by
- 68
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 3 · 2017: 8 · 2016: 9 · 2015: 4 · 2014: 7 · 2013: 3 · 2012: 7
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Canada's Michael Smith Genome Sciences Centre
- Stiftelsen för Strategisk Forskning
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Uppsala Universitet
- BC Cancer Agency
- 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
- HNF4α, FOXA2, GABP, transcription factor binding sites, transcription factor interaction, distal regulatory elements, transcription start sites, USF1, USF2, co-immunoprecipitation
- MeSH terms
- Binding Sites, Humans, Liver, Gene Expression, Sequence Alignment, Conserved Sequence, Sequence Analysis, DNA, Polymorphism, Single Nucleotide, Transcription Initiation Site, Chromatin Immunoprecipitation, Regulatory Elements, Transcriptional, GA-Binding Protein Transcription Factor, Hepatocyte Nuclear Factor 3-beta, Hepatocyte Nuclear Factor 4, Upstream Stimulatory Factors
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