Structural and functional characterisation of a cell cycle associated HDAC1/2 complex reveals the structural basis for complex assembly and nucleosome targeting.

Recent proteomic studies have identified a novel histone deacetylase complex that is upregulated during mitosis and is associated with cyclin A. This complex is conserved from nematodes to man and contains histone deacetylases 1 and 2, the MIDEAS corepressor protein and a protein called DNTTIP1 whose function was hitherto poorly understood. Here we report the structures of two domains from DNTTIP1. The aminoterminal region forms a tight dimerisation domain with a novel structural fold that interacts with and mediates assembly of the HDAC1:MIDEAS complex. The carboxyterminal domain of DNTTIP1 has a structure related to the SKI/SNO/DAC domain, despite lacking obvious sequence homology. We show that this domain in DNTTIP1 mediates interaction with both DNA and nucleosomes. Thus DNTTIP1 acts as a dimeric chromatin binding module in the HDAC1:MIDEAS corepressor complex.