Kevin Li L&S Biological Sciences
Probing chromatin-binding dynamics of PRC2, a key epigenetic regulator
Polycomb Repressive Complex 2 (PRC2) is a key epigenetic regulator complex that acts as a gene silencer to maintain cell identity, depositing the repressive histone H3 K27 trimethylation mark at target genes. Faulty PRC2 regulation is involved in developmental disorders and cancer development, but mechanisms that direct PRC2 activity to target genes are poorly understood. Recent structural findings show PRC2 binding through its catalytic lobe, but do not provide a mechanism to explain how PRC2 localizes to target sites in vitro without its catalytic lobe. To address this knowledge gap, I will systematically perturb several chromatin-binding surfaces in both catalytic and non-catalytic lobes, and then use live cell imaging and single-particle tracking to determine the contribution of each surface to chromatin-binding dynamics. These findings will be valuable in understanding the regulatory mechanisms at play in PRC2 and enable further studies on its localization and catalytic function.