Structural Insights into the regulation of the gene silencer PRC2

Polycomb repressive complex 2 (PRC2) is an epigenetic regulator that modifies histone
H3 by trimethylation of lysine 27 (H3K27me3). Spreading of the H3K27me3 mark
ultimately results in chromatin compaction and leads to the repression of the underlying
genes. PRC2 activity is essential during embryonic development and to maintain cell
identity in adulthood, with mutations and/or misregulation of PRC2 leading to cancer.
We have studied the molecular principles underlying regulation of the core PRC2 by
cofactors and by histone modifications. Recently, it has been shown that PRC2
undergoes auto-methylation within its catalytic SET domain, which results in stimulation
of its function by an unknown mechanism. Using cryo-electron microscopy, optimized
for fragile complexes, we have been able to obtain structural information that leads to a
novel mechanism of auto-regulation by an epigenetic factor.

All seminars will be held at noon at the Gordon Center for Integrative Science W301.