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PMID: 19822575 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular interactions between HNF4a, FOXA2 and GABP identified at regulatory DNA elements through ChIP-sequencing.

Nucleic acids research ·Vol. 37 ·No. 22 ·2009-12-00 ·Pages 7498-508

Wallerman O, Motallebipour M, Enroth S, Patra K, Bysani MS, Komorowski J, Wadelius C

Abstract

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.

MeSH Terms
Binding Sites Chromatin Immunoprecipitation Conserved Sequence GA-Binding Protein Transcription Factor/analysis,metabolism Gene Expression Hepatocyte Nuclear Factor 3-beta/analysis,metabolism Hepatocyte Nuclear Factor 4/analysis,metabolism Humans Liver/metabolism Polymorphism, Single Nucleotide Regulatory Elements, Transcriptional Sequence Alignment Sequence Analysis, DNA Transcription Initiation Site Upstream Stimulatory Factors/analysis
Chemicals
FOXA2 protein, human GA-Binding Protein Transcription Factor HNF4A protein, human Hepatocyte Nuclear Factor 4 Upstream Stimulatory Factors Hepatocyte Nuclear Factor 3-beta
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wallerman Ola
Department of Genetics and Pathology, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden.
Motallebipour Mehdi
Enroth Stefan
Patra Kalicharan
Bysani Madhu Sudhan Reddy
Komorowski Jan
Wadelius Claes
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkp823
Published
2009-12-00
Pages
7498-508
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2794179
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkp823 PMC Full Text View journal details
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