Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing.
Foxa2 (HNF3 beta) 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 approximately 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.
Wederell
Elizabeth D
ED
Terry Fox Laboratory, BC Cancer Agency, Vancouver, Canada.
Bilenky
Mikhail
M
Cullum
Rebecca
R
Thiessen
Nina
N
Dagpinar
Melis
M
Delaney
Allen
A
Varhol
Richard
R
Zhao
YongJun
Y
Zeng
Thomas
T
Bernier
Bridget
B
Ingham
Matthew
M
Hirst
Martin
M
Robertson
Gordon
G
Marra
Marco A
MA
Jones
Steven
S
Hoodless
Pamela A
PA
D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D005260:Female; D015870:Gene Expression; D053263:Gene Regulatory Networks; D023281:Genomics; D051542:Hepatocyte Nuclear Factor 3-beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
C496503:Foxa2 protein, mouse; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta