ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity

Abstract

Transcriptional control is dependent on a vast net-work of epigenetic modifications. One epigenetic mark of particular interest is tri-methylation of lysine 27 on histone H3 (H3K27me3), which is cata-lysed and maintained by Polycomb Repressive Complex 2 (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 canon-ical view of H3K27me3 as inhibitory to transcription. Second, a peak of enrichment around the transcrip-tion start site (TSS) 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 stu-died. The data analysis techniques developed here will be useful for the identification of common en-richment profiles for other histonemodifications that have important consequences for transcriptional regulation