FOX proteins are predicted to bind to putative <i>let-7a3/b</i> enhancer regions.

Abstract

<p><b>(A)</b> The predicted existence of an upstream enhancer for the <i>let-7a3/b</i> locus was based on the epigenetic state at a region 10kb upstream of the TSS, outlined in green. In addition to being marked by H3K27Ac ChIP-Seq peaks with a localized dip in signal intensity, and peaks for the enhancer-associated histone acetyltransferase protein P300, this region showed dynamic changes in DNAse sensitivity. Note that a large DNAse sensitivity peak appears only in ES-derived NPCs, suggesting a differentiation state-specific chromatin opening at this region. At bottom, relative intensity of forkhead box protein ChIP-Seq from multiple cell types are pooled, with the darkest regions indicating intense FOX protein binding. Outlined in red are similar regions that show DNAse sensitivity beginning at the fetal brain stage that also colocalize with FOX protein binding. <b>(B)</b> A zoomed in view of the green region of increased DNAse sensitivity in PSC-derived NPCs. In blue are computationally predicted transcription factor binding sites from the ORCAtk database. The degree of genomic conservation along this region from the PhastCons64 database is shown in purple. At bottom are transcription factor ChIP-seq mapped peaks from the ENCODE database. The regions in green mark forkhead box transcription factor conserved motifs. Note that the forkhead box motifs co-localize with a region of highly conserved sequence, and the redundant binding of the forkhead box motif by many family members predicts that many such proteins can bind there.</p

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