Curtis Beck Rose Hills
Investigating the Functional Crosstalk Between the Crucial Epigenetic Silencers PRC1 and PRC2
In mammals, the Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) play crucial roles in maintaining gene expression patterns that enforce cell differentiation during embryonic development. Both complexes silence genes by post-translationally modifying the histone tails of nucleosomes, the smallest structural unit of chromatin. PRC1 plays a role in chromatin compaction by histone ubiquitination, whereas PRC2 reduces expression at the transcriptional level by histone methylation. The importance of these two complexes is emphasized by the fact that mutations in either complex results in embryonic lethality. While PRC1 and PRC2 are essential in maintaining cell identity, the molecular mechanism of PRC1-mediated chromatin compaction and the spreading of silencing marks by PRC2 remains poorly understood. Using cryo-electron microscopy and a novel technique to prevent the denaturation of sensitive protein complexes, we will directly image PRC2-nucleosome interactions to investigate the mechanisms underlying the recognition of specific histone ubiquitination by PRC2 and how it affects PRC2s methyltransferase activity. Our goal is to provide atomic-resolution structures of PRC1 and PRC2, providing insight into the crosstalk between two crucial gene-silencing enzymes.