Post-translational modification of histones plays a central role in chromatin remodelling. Trimethylation of histone H3 at lysine 4 (H3K4me3) is associated with active gene transcription, whereas trimethylation at H3K27 is associated with repression. Which enzyme complex catalyses H3K27 trimethylation and thereby maintains transcriptional silencing of developmental genes?

• A Polycomb repressive complex 2 (PRC2) containing EZH2 histone methyltransferase ✓
• B COMPASS complex containing SET1 histone methyltransferase
• C NuRD complex containing HDAC1/2
• D SWI/SNF complex containing BRG1 ATPase

Explanation

PRC2 (Polycomb repressive complex 2) uses its catalytic subunit EZH2 (a SET-domain histone methyltransferase) to trimethylate H3K27, creating a repressive mark. H3K27me3 recruits PRC1, which ubiquitinates H2AK119 and compacts chromatin, silencing developmental genes until needed. COMPASS/SET1 performs H3K4 methylation (activation). NuRD contains HDACs that remove acetyl marks (repression, but not by methylation). SWI/SNF is an ATP-dependent nucleosome remodeller that generally activates transcription. EZH2 gain-of-function mutations are oncogenic in B-cell lymphomas.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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