Vignesh Kasinath

We are primarily interested in the structural and mechanistic basis for how epigenetics changes in chromatin regulate transcription repression and heterochromatin formation. 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. 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.

In addition to the Polycomb system, we are also interested in characterizing the molecular basis of the hierarchy of events leading to the formation of heterochromatin. What are the structural and functional basis for the different chromatin modifier complexes involved in heterochromatin formation? What is the molecular basis for the local and global chromatin architecture during heterochromatin formation? We adopt a multi-disciplinary approach involving cryo-EM, mass spectrometry, biochemical approaches and in situ studies.

• Kasinath, V., Beck, C., Sauer, P., Poepsel, S., Kosmatka, J., Faini, M., Toso, D., Aebersold, R., and Nogales. E. JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Science (2021) doi: https://doi.org/10.1126/science.abc3393
• Kasinath, V., Faini M, Poepsel S, Reif, D., Feng, XA., Stjepanovic, G., Aebersold, R., and Nogales, E. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science (2018)
• Poepsel, S., Kasinath, V., and Nogales, E. Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. Nat. Struct. Mol. Biol. (2018)