H3K27me3

H3K27me3 stands for histone H3 lysine 27 trimethylation, a repressive epigenetic modification found on histone H3. It is deposited primarily by the Polycomb repressive complex 2 (PRC2), whose core components include the methyltransferases EZH2 (or EZH1) along with SUZ12, EED, and RBBP4/7. The trimethylation mark promotes a compact chromatin state, leading to transcriptional silencing at target loci, particularly at developmental regulatory genes and regulatory elements.

In development, H3K27me3 helps maintain genes in an off state in stem cells and differentiating lineages. Some genes carry bivalent domains that contain both H3K27me3 and the activating mark H3K4me3, allowing them to be poised for activation upon differentiation. The mark can be erased by histone demethylases KDM6A (UTX) and KDM6B (JMJD3), enabling gene activation. PRC1 can recognize H3K27me3 and further reinforce repression through ubiquitination of H2AK119, contributing to chromatin compaction and stable silencing.

Distribution of H3K27me3 is often broad over regulatory regions or gene clusters rather than isolated peaks, reflecting its role in coordinating large-scale gene silencing. Its patterns are dynamic during development and in response to cellular signals. Abnormal H3K27me3 regulation is linked to diseases such as cancer and developmental disorders. Detection and study of this mark commonly use chromatin immunoprecipitation followed by sequencing (ChIP-seq) or alternative methods like CUT&RUN. Pharmacological inhibition of EZH2, a key writer of this mark, is an active area of cancer therapy research.