Acquired tissue-specific promoter bivalency is a basis for PRC2 necessity in adult somatic cells

To define H3K27me3 modified genes in intestinal stem, progenitor and epithelial cells, we performed chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq). We used RNA-sequencing to profile gene expression changes during intestinal stem cell differentiation into mature villus cells, as well as genes perturbed upon loss of PRC2 activity (deletion of Eed) . We find thousands of genes that change in expression including many H3K27me3 marked genes. The deregulated genes reaveal a intestinal tissue specific role of PRC2. Overall design: H3K27me3, H3K4me2 and RNA Pol2 ChIP-Seq analysis of isolated mouse intestinal stem cells, enterocyte and secretory progenitor cells, and mature villus cells. RNA seq analysis of control mouse villus cells, control intestinal stem cells and Eed-deleted villus.

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Jadhav U, Nalapareddy K, Saxena M, O'Neill NK, Pinello L, Yuan GC, Orkin SH, Shivdasani RA