ResearchPolycomb repressive complexes play important roles in numerous processes including developmental gene regulation, stem cell self-renewal and differentiation, and in the development and recurrence of cancer.
Polycomb group proteins are components of multi-protein complexes and are divided into two evolutionary distinct groups based on their ability to post translationally modify chromatin.
The Polycomb Repressive Complex 2 (PRC2) contains the methyl-transferase Ezh2 and tri-methylates lysine 27 of histone H3 (H3K27me3).
The Polycomb Repressive Complex 1 (PRC1) contains the E3 ubiquitin ligases Ring1A/Ring1B and mono-ubiquitylates lysine 119 of histone H2A (H2AK119u1).
Both histone modifications H3K27me3 and H2AK119u1 are associated with gene repression. In Embryonic Stem (ES) cells developmental gene promoters are maintained in a “poised” state.
These promoters have active histone modifications (H3K4me3), as well as repressive histone modifications (H3K27me3 and H2AK119u1) established by PRC complexes. This chromatin state is known as bivalent chromatin.
On differentiation bivalent promoters are resolved into active or repressed chromatin states leading to cell fate decisions. In lineage specific progenitors a small number of bivalent promoters are not resolved and remain poised for further lineage specification.
Our lab is focused on understanding how Polycomb complexes are recruited to chromatin and the fundamental mechanisms underpinning Polycomb mediated gene repression: