Professor John Schwabe, Department Molecular and Cell Biology, University of Leicester
Tuesday 8th November, 1.00 p.m., Stacey Lecture Theatre 1
My group is seeking to understand the molecular mechanisms that underlie the epigentic reprogramming of the genome during cellular differentiation and development. At least five large, multiprotein Histone Deacetylase (HDAC) complexes are key players. They trigger the programmed repression of regions of the genome which is one of the critical first steps. Interestingly these complexes also play a role in the expression of active genes.
We have led the field in using crystallographic studies to explore the assembly of the SMRT:HDAC3:TBL1:GPS2 complex, the NuRD complex HDAC1:MTA1:RBBP4 and the MiDAC complex. These studies led to the unexpected and breakthrough discovery that HDAC complexes are regulated by small molecule inositol phosphates.
More recently we have taken an integrated approach combining crystal structures with cross-linking/mass spectrometry, SAXS and negative stain EM to build a more complete picture of these complexes.
We are now working towards cryo-EM structures for the NuRD (750 kDa), MIDAC (450kDa), CoREST (200kDa), Sin3A (260kDa) and SMRT (420kDa) complexes.