Cis-regulatory modules in the mammalian liver: Composition depends on strength of Foxa2 consensus site

Department of Genetics, Genomics and Computational Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Nucleic Acids Research (Impact Factor: 9.11). 08/2008; 36(12):4149-57. DOI: 10.1093/nar/gkn366
Source: PubMed

ABSTRACT 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.

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Available from: Klaus H Kaestner, Aug 20, 2015
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    • "nsus binding sequence were at genes that are much more liver - specific than genes with a strong consensus sequence ( Tuteja et al . 2008 ) . Simple target site affinity was not a predictor of FoxA occupancy , at least in terminally differentiated cells . While the nature of this is discussed in detail below ( and see also Hoffman et al . 2010 ) , Tuteja et al . ( 2008 ) did find that medium - and lower - affinity , liver - specific targets were highly enriched for binding of other hepatic nuclear fac - tors , suggesting a role for cooperative binding during the maintenance of differentiation . Furthermore , in adult liver tissue , FoxA1 and FoxA2 binding was not required to maintain local nucleosome "
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