title: Structural Insight into Recognition of Methylated Histone H3K4 by Set3.
abstract: The plant homeodomain (PHD) finger of Set3 binds methylated lysine 4 of histone H3 in vitro and in vivo; however, precise selectivity of this domain has not been fully characterized. Here, we explore the determinants of methyllysine recognition by the PHD fingers of Set3 and its orthologs. We use X-ray crystallographic and spectroscopic approaches to show that the Set3 PHD finger binds di- and trimethylated states of H3K4 with comparable affinities and employs similar molecular mechanisms to form complexes with either mark. Composition of the methyllysine-binding pocket plays an essential role in determining the selectivity of the PHD fingers. The finding that the histone-binding activity is not conserved in the PHD finger of Set4 suggests different functions for the Set3 and Set4 paralogs.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Jovylyn
authors.initials: J
authors.lastname: Gatchalian
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: Forest H
authors.initials: FH
authors.lastname: Andrews
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Structural Biology and Biochemistry Program, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Barrett
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Structural Biology and Biochemistry Program, 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: D018360:Crystallography, X-Ray; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D006657:Histones; D006655:Histone Deacetylases; D008239:Lysine
keywords: PHD finger; Set3; Set4; histone; methylation