title: Diverse functions of PHD fingers of the MLL/KMT2 subfamily.
abstract: Five members of the KMT2 family of lysine methyltransferases, originally named the mixed lineage leukemia (MLL1-5) proteins, regulate gene expression during embryogenesis and development. Each KMT2A-E contains a catalytic SET domain that methylates lysine 4 of histone H3, and one or several PHD fingers. Over the past few years a growing number of studies have uncovered diverse biological roles of the KMT2A-E PHD fingers, implicating them in binding to methylated histones and other nuclear proteins, and in mediating the E3 ligase activity and dimerization. Mutations in the PHD fingers or deletion of these modules are linked to human diseases including cancer and Kabuki syndrome. In this work, we summarize recently identified biological functions of the KMT2A-E PHD fingers, discuss mechanisms of their action, and examine preference of these domains for histone and non-histone ligands.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Ali
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hom
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Weston
authors.initials: W
authors.lastname: Blakeslee
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Larissa
authors.initials: L
authors.lastname: Ikenouye
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: Tatiana.Kutateladze@ucdenver.edu.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones
keywords: Chromatin; Histone; KMT2; MLL; Methyltransferase; PHD finger