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

  • Nucleic Acids Res. 2015 Feb 27;43(4):2033-44. doi: 10.1093/nar/gkv068.
Toshimasa Itoh  1 ,  Louise Fairall  1 ,  Frederick W Muskett  1 ,  Charles P Milano  1 ,  Peter J Watson  1 ,  Nadia Arnaudo  2 ,  Almutasem Saleh  1 ,  Christopher J Millard  1 ,  Mohammed El-Mezgueldi  1 ,  Fabrizio Martino  2 ,  John W R Schwabe  3
Affiliations
  • 1. Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
  • 2. MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
  • 3. Henry Wellcome Laboratories of Structural Biology, Department of Biochemistry, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK [email protected].
PMID: 25653165 DOI: 10.1093/nar/gkv068
Abstract

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 amino-terminal region forms a tight dimerization domain with a novel structural fold that interacts with and mediates assembly of the HDAC1:MIDEAS complex. The carboxy-terminal 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.