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

Véronique Tremblay, Pamela Zhang, Chandra Prakash Chaturvedi, Janet Thornton, Joseph S. Brunzelle, Georgios Skiniotis, Ali Shilatifard, Marjorie Brand, Jean François Couture*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1821-1830
Number of pages10
JournalStructure
Volume22
Issue number12
DOIs
StatePublished - Dec 2 2014

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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