Molecular basis for DPY-30 association to COMPASS-like and NURF complexes

Structure. 2014 Dec 2;22(12):1821-1830. doi: 10.1016/j.str.2014.10.002. Epub 2014 Nov 20.

Abstract

DPY-30 is a subunit of mammalian COMPASS-like complexes (complex of proteins associated with Set1) and regulates global histone H3 Lys-4 trimethylation. Here we report structural evidence showing that the incorporation of DPY-30 into COMPASS-like complexes is mediated by several hydrophobic interactions between an amphipathic α helix located on the C terminus of COMPASS subunit ASH2L and the inner surface of the DPY-30 dimerization/docking (D/D) module. Mutations impairing the interaction between ASH2L and DPY-30 result in a loss of histone H3K4me3 at the β locus control region and cause a delay in erythroid cell terminal differentiation. Using overlay assays, we defined a consensus sequence for DPY-30 binding proteins and found that DPY-30 interacts with BAP18, a subunit of the nucleosome remodeling factor complex. Overall, our results indicate that the ASH2L/DPY-30 complex is important for cell differentiation and provide insights into the ability of DPY-30 to associate with functionally divergent multisubunit complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Crystallography, X-Ray
  • DNA-Binding Proteins / metabolism*
  • Escherichia coli
  • Models, Molecular*
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / metabolism*

Substances

  • ASH2L protein, human
  • DNA-Binding Proteins
  • DPY30 protein, human
  • Nuclear Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors

Associated data

  • PDB/4RIQ