TY - JOUR
T1 - Molecular basis for DPY-30 association to COMPASS-like and NURF complexes
AU - Tremblay, Véronique
AU - Zhang, Pamela
AU - Chaturvedi, Chandra Prakash
AU - Thornton, Janet
AU - Brunzelle, Joseph S.
AU - Skiniotis, Georgios
AU - Shilatifard, Ali
AU - Brand, Marjorie
AU - Couture, Jean François
N1 - Funding Information:
J.F.C. is supported by a CIHR grant (MOP-136816) and acknowledges an Early Research Award from MEDI and a Canada Research Chair in Structural Biology and Epigenetics. P.Z. holds a Banting & Best Ph.D. scholarship. M.B. acknowledges a CIHR grant (MOP-89834). G.S. acknowledges support from the Pew Scholars Program in Biomedical Sciences. The studies performed by the A.S. laboratory are supported by NIH grant R01GM069905.
Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2014/12/2
Y1 - 2014/12/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.str.2014.10.002
DO - 10.1016/j.str.2014.10.002
M3 - Article
C2 - 25456412
AN - SCOPUS:84914097368
SN - 0969-2126
VL - 22
SP - 1821
EP - 1830
JO - Structure
JF - Structure
IS - 12
ER -