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. Epub 2015 Feb 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Co-Repressor Proteins / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins
  • HEK293 Cells
  • Histone Deacetylase 1 / metabolism*
  • Histone Deacetylase 2 / metabolism
  • Humans
  • Models, Molecular
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Nucleosomes / metabolism*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Transcription Factors

Substances

  • Carrier Proteins
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • DNTTIP1 protein, human
  • MIDEAS protein, human
  • Nuclear Proteins
  • Nucleosomes
  • Transcription Factors
  • DNA
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylase 2

Associated data

  • PDB/4D6K