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Nucleic Acids Research Advance Access published online on July 8, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn382
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing

Elizabeth D. Wederell1, Mikhail Bilenky2, Rebecca Cullum1, Nina Thiessen2, Melis Dagpinar2, Allen Delaney2, Richard Varhol2, YongJun Zhao2, Thomas Zeng2, Bridget Bernier2, Matthew Ingham2, Martin Hirst2, Gordon Robertson2, Marco A. Marra2, Steven Jones2 and Pamela A. Hoodless1,*

1Terry Fox Laboratory and 2Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, Canada

*To whom correspondence should be addressed. Tel: +604 675 8133; Fax: +604 877 0712; Email: hoodless{at}bccrc.ca

Received April 14, 2008. Revised May 13, 2008. Accepted May 30, 2008.

Foxa2 (HNF3β) is a one of three, closely related transcription factors that are critical to the development and function of the mouse liver. We have used chromatin immunoprecipitation and massively parallel Illumina 1G sequencing (ChIP–Seq) to create a genome-wide profile of in vivo Foxa2-binding sites in the adult liver. More than 65% of the ~11.5 k genomic sites associated with Foxa2 binding, mapped to extended gene regions of annotated genes, while more than 30% of intragenic sites were located within first introns. 20.5% of all sites were further than 50 kb from any annotated gene, suggesting an association with novel gene regions. QPCR analysis demonstrated a strong positive correlation between peak height and fold enrichment for Foxa2-binding sites. We measured the relationship between Foxa2 and liver gene expression by overlapping Foxa2-binding sites with a SAGE transcriptome profile, and found that 43.5% of genes expressed in the liver were also associated with Foxa2 binding. We also identified potential Foxa2-interacting transcription factors whose motifs were enriched near Foxa2-binding sites. Our comprehensive results for in vivo Foxa2-binding sites in the mouse liver will contribute to resolving transcriptional regulatory networks that are important for adult liver function.


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