VIGNESH KASINATH LAB

Our recent work provided a physical basis for how PRC2 could be recruited to chromatin through the recognition of monoubiquitination of histone H2A at lysine 119 (H2AK119ub1). H2AK119ub1 deposition, however, is carried out by PRC1. PRC1 complexes are broadly divided into two classes: variant or non-canonical PRC1, and canonical PRC1. The variant PRC1 complexes are thought to be responsible for the vast majority of H2AK119ub1 deposition while canonical PRC1’s principal role is attributed to chromatin compaction through the recognition of PRC2-mediated H3K27me3.

We seek to answer fundamental questions concerning

1. Mechanistic basis for the functional differences between different PRC1 complexes

2. Recruitment of PRC1 to chromatin

3. Physical basis for the chromatin compaction activity of canonical PRC1

We are primarily interested in the structural and mechanistic basis for how chromatin modifiers regulate gene expression. Polycomb Repressive Complex is a key regulator of gene expression patterns during embryonic stem cell development and vital for maintaining gene expression patterns post-differentiation. Polycomb Repressive Complex controls the transcriptional on- or off-state of genes in all cell types allowing for the regulated temporal control of gene expression. Polycomb complexes maintain in a transcriptionally repressed state those subset of genes that are not critical in a specific cell-type through the formation of heterochromatin bodies known as Polycomb bodies. Some of the questions we seek answers concern the mechanistic basis for the cascade of events leading to the formation of Polycomb bodies as well as the functional roles of different Polycomb complexes.

Video Animations of our previous work can be viewed below.