The Polycomb Repressive Complex 2 (PRC2) plays a critical role in maintaining cellular identity during cell fate transitions in differentiation and development. PRC2 consists of a trimeric core of SUZ12, EED, and EZH1/2, which catalyse methylation of histone H3 at lysine 27 (H3K27me1/2/3). The histone methyltransferase activity of PRC2 is deregulated in several cancers and certain developmental disorders, such as Weaver Syndrome.
PRC2 organises into two distinct subcomplexes, PRC2.1 and PRC2.2, each distinguished by a unique set of accessory proteins, including Polycomb-like proteins, JARID2, and AEBP2. Our previous work demonstrated that, while both subcomplexes target the same genes, they are recruited through different mechanisms and regulate the recruitment of distinct forms of canonical PRC1 to mediate transcriptional repression.
In this talk, I’ll present some unpublished findings from our lab, revealing new insights into how these PRC2 subcomplexes and their accessory proteins shape development and contribute to disease.