Cis-regulatory modules in the mammalian liver: composition depends on strength of Foxa2 consensus site.
Foxa2 is a critical transcription factor that controls liver development and plays an important role in hepatic gluconeogensis in adult mice. Here, we use genome-wide location analysis for Foxa2 to identify its targets in the adult liver. We then show by computational analyses that Foxa2 containing cis-regulatory modules are not constructed from a random assortment of binding sites for other transcription factors expressed in the liver, but rather that their composition depends on the strength of the Foxa2 consensus site present. Genes containing a cis-regulatory module with a medium or weak Foxa2 consensus site are much more liver-specific than the genes with a strong consensus site. We not only provide a better understanding of the mechanisms of Foxa2 regulation but also introduce a novel method for identification of different cis-regulatory modules involving a single factor.
Department of Genetics, Genomics and Computational Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Geetu
G
Tuteja
Shane T
ST
Jensen
Peter
P
White
Klaus H
KH
Kaestner
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D016384:Consensus Sequence; D023281:Genomics; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D050436:Regulatory Elements, Transcriptional; D014157:Transcription Factors / Q000378:metabolism
C496503:Foxa2 protein, mouse; D014157:Transcription Factors; D051542:Hepatocyte Nuclear Factor 3-beta