Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver
| Autor: | Sam Lee, Mikhail Bilenky, Pamela A. Hoodless, Marco A. Marra, Rebecca Cullum, Brad G. Hoffman, Derek L. Dai, Leping Li, Elizabeth D. Wederell, Cheryl D. Helgason, Gordon Robertson, Angela Tam, Martin Hirst, Nina Thiessen, Steven J.M. Jones, Inanc Birol, Baljit Kamoh, Mike Beach, Bogard Zavaglia, Galina Soukhatcheva, Yongjun Zhao, C. Bruce Verchere, Timothee Cezard |
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| Rok vydání: | 2010 |
| Předmět: |
endocrine system
Molecular Sequence Data Response element Regulatory Sequences Nucleic Acid Biology Histones Islets of Langerhans Mice Sp3 transcription factor Genetics Animals Enhancer Genetics (clinical) Homeodomain Proteins Binding Sites Base Sequence General transcription factor Gene Expression Profiling Research Eukaryotic transcription Promoter TCF4 Nucleosomes Cell biology Hepatocyte Nuclear Factor 4 Liver Genetic Loci TAF2 Hepatocyte Nuclear Factor 3-beta Trans-Activators |
| Zdroj: | Genome Research. 20:1037-1051 |
| ISSN: | 1088-9051 |
| Popis: | The liver and pancreas share a common origin and coexpress several transcription factors. To gain insight into the transcriptional networks regulating the function of these tissues, we globally identify binding sites for FOXA2 in adult mouse islets and liver, PDX1 in islets, and HNF4A in liver. Because most eukaryotic transcription factors bind thousands of loci, many of which are thought to be inactive, methods that can discriminate functionally active binding events are essential for the interpretation of genome-wide transcription factor binding data. To develop such a method, we also generated genome-wide H3K4me1 and H3K4me3 localization data in these tissues. By analyzing our binding and histone methylation data in combination with comprehensive gene expression data, we show that H3K4me1 enrichment profiles discriminate transcription factor occupied loci into three classes: those that are functionally active, those that are poised for activation, and those that reflect pioneer-like transcription factor activity. Furthermore, we demonstrate that the regulated presence of H3K4me1-marked nucleosomes at transcription factor occupied promoters and enhancers controls their activity, implicating both tissue-specific transcription factor binding and nucleosome remodeling complex recruitment in determining tissue-specific gene expression. Finally, we apply these approaches to generate novel insights into how FOXA2, PDX1, and HNF4A cooperate to drive islet- and liver-specific gene expression. |
| Databáze: | OpenAIRE |
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