H3K27

H3K27 refers to the lysine 27 residue on histone H3, a site on the N-terminal tail that can be modified by methylation or acetylation. These chemical marks influence chromatin structure and gene activity, helping to regulate transcription across development and differentiation.

Methylation at H3K27 is primarily carried out by the Polycomb Repressive Complex 2 (PRC2), with EZH2 as the catalytic subunit (and EZH1 in some contexts). H3K27 can be mono-, di-, or trimethylated (H3K27me1/2/3), with H3K27me3 serving as a hallmark of facultative heterochromatin and transcriptional repression. This mark is recognized by other Polycomb components, including PRC1, which helps compact chromatin and maintain silenced states. Demethylases such as KDM6A (UTX) and KDM6B (JMJD3) can remove methyl groups, enabling gene activation during development or in response to signals. In embryonic stem cells, genes important for development often exhibit bivalent domains containing both H3K27me3 and the activating mark H3K4me3, signifying poised regulation.

Acetylation at H3K27 (H3K27ac) marks active regulatory elements, particularly enhancers and, to a lesser extent, promoters. This modification is deposited by histone acetyltransferases such as CBP and p300 and is associated with open chromatin and transcriptional activation. Deacetylation by histone deacetylases can reverse the mark, contributing to dynamic regulation of gene expression. The balance between H3K27me3 and H3K27ac influences developmental gene programs and cell fate decisions.

Biological significance includes roles in development, X-chromosome inactivation, and cancer. Experimental methods to study H3K27 modifications include chromatin immunoprecipitation followed by sequencing (ChIP-seq) and related approaches like CUT&RUN.