title: Molecular basis for DPY-30 association to COMPASS-like and NURF complexes.
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.
authors.affiliation: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
authors.forename: Véronique
authors.initials: V
authors.lastname: Tremblay
authors.affiliation: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Zhang
authors.affiliation: The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
authors.forename: Chandra-Prakash
authors.initials: CP
authors.lastname: Chaturvedi
authors.affiliation: Department of Biochemistry and Molecular Genetics, Northwestern University, Searle Building, 320 East Superior Street, Chicago, IL 60611, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Thornton
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Brunzelle
authors.affiliation: Life Sciences Institute and Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Skiniotis
authors.affiliation: Department of Biochemistry and Molecular Genetics, Northwestern University, Searle Building, 320 East Superior Street, Chicago, IL 60611, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
authors.affiliation: The Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8L6, Canada.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Brand
authors.affiliation: Ottawa Institute of Systems Biology, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada. Electronic address: jean-francois.couture@uottawa.ca.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Couture
mesh_terms: D002460:Cell Line; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C485622:ASH2L protein, human; D004268:DNA-Binding Proteins; C507432:DPY30 protein, human; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors