title: Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes.
abstract: MLL complexes are homologs of yeast COMPASS capable of methylating histone H3 Lys4 (H3K4). ASH2L, RbBP5 and WDR5 are conserved subunits of MLL complexes with homology to the Cps40/Cps60, Cps50 and Cps30 subunits of COMPASS, respectively. We report that ASH2L differentially regulates MLL's catalysis of H3K4 trimethylation similarly to Cps40 and Cps60. Furthermore, WDR5 is required to maintain MLL complex integrity, including the stability of ASH2L within the complex. These findings offer insight into the molecular role of ASH2L, and by extension that of WDR5, in proper H3K4 trimethylation.
authors.affiliation: Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Blvd., St. Louis, Missouri 63104, USA.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Steward
authors.forename: Jung-Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Aisling
authors.initials: A
authors.lastname: O'Donovan
authors.forename: Matt
authors.initials: M
authors.lastname: Wyatt
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Bernstein
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008954:Models, Biological; D051788:Myeloid-Lymphoid Leukemia Protein / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C485622:ASH2L protein, human; D004268:DNA-Binding Proteins; D006657:Histones; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D021122:Protein Subunits; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine