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Chunk #26 — Simple combinations of binding sites identify cell type-specific repertoires of H3K4me1-marked regions

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Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities.
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To determine whether there is an analogous relationship between promoter-distal H3K4me1 and binding sites for transcription factors in other cell types, we performed de novo motif analysis on H3K4me1/H3K4me3 ChIP-Seq data sets from mouse embryonic stem cells (Meissner et al., 2008; Mikkelsen et al., 2007), liver (Wederell et al., 2008), human CD4+ T cells (Barski et al., 2007) and CD36+ erythrocyte precursors (Cui et al., 2009). Similar to the results in macrophages and B cells, H3K4me1-marked promoter-distal regions in these tissues were highly enriched for motifs for transcription factors required for the generation and maintenance of each cellular phenotype (Ivanova et al., 2006; Rothenberg and Taghon, 2005; Zaret et al., 2008) (Figure S4C). For example, H3K4me1-marked promoter-distal regions in ES cells were significantly enriched for binding sites for KLF4, OCT4, SOX2 and Esrrβ, factors that in combination are sufficient to reprogram somatic cells into induced pluripotent stem cells (Feng et al., 2009). In CD4+ T cells, this analysis revealed a strong association of H3K4me1-marked regions with Ets and Runx motifs, consistent with their known essential roles in T cell development