ChIP-seq analysis reveals distinct H3K27me3 profiles associated with gene regulation [ChIP-seq]

Transcriptional control is dependent on a vast network of epigenetic modifications. One epigenetic mark of particular interest is tri-methylation of lysine 27 on histone H3 (H3K27me3), which is catalyzed and maintained by the Polycomb Repressor Complex (PRC2). Although this histone mark is studied widely, the precise relationship between its local pattern of enrichment and regulation of gene expression is currently unclear. We have used ChIP-seq to generate genome wide maps of H3K27me3 enrichment, and have identified three enrichment profiles with distinct regulatory consequences. First, a broad domain of H3K27me3 enrichment across the body of genes corresponds to the canonical view of H3K27me3 as inhibitory to transcription. Second, a peak of enrichment around the transcription start site is commonly associated with “bivalent” genes, where H3K4me3 also marks the TSS. Finally and most surprisingly, we identified an enrichment profile with a peak in the promoter of genes that is associated with active transcription. Genes with each of these three profiles were found in different proportions in each of the cell types studied. The data analysis techniques developed here will be useful for the identification of common enrichment profiles for other histone modifications that have important consequences for transcriptional regulation. Genomic DNA was extracted from ES cells and G1ME cells in mouse. ChIP-seq with antibodies for H3K27me3, RNApol-II were run for both cell types. As a control, whole cell extract or Input DNA was also sequenced for both cell types without the inclusion of an antibody.