Foxa2-Specific Targets Contain a Medium-Strength <i>Forkhead</i> Consensus and Control Genes in Steroid and Lipid Metabolism.

<p>(A) The motifs found by <i>de novo</i> analysis for both Foxa2-only bound set (yellow circle) resemble a <i>forkhead</i> binding site. Intersection of Foxa2-bound regions and genes differentially expressed in livers of Foxa2-deficient mice (light purple circle) identified three-hundred thirty-three direct targets. (B) Validation of Foxa2-only targets by qPCR. Filled bars, ChIP of liver chromatin with an anti-Foxa1 antibody, open bars, ChIP with an anti-Foxa2 antibody. Binding is expressed as enrichment of the PCR amplicon relative to input DNA in liver chromatin. Negative controls (Nc1, Nc2, Nc3) are regions with a low amount of reads. (C) Foxa2 targets are enriched in genes involved in lipid and steroid metabolism, protein modification, and carbohydrate metabolism. (D) Histogram of the distribution of Foxa2-only sites relative to TSS. Foxa2-only sites, similar to the Foxa1/Foxa2 dual targets (compare <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002770#pgen-1002770-g004" target="_blank">Figure 4E</a>), are distributed normally near transcription start sites (TSS), with most sites within ten kilobases (Kb) from TSS.