title: Recognition of Histone H3K14 Acylation by MORF.
abstract: The monocytic leukemia zinc-finger protein-related factor (MORF) is a transcriptional coactivator and a catalytic subunit of the lysine acetyltransferase complex implicated in cancer and developmental diseases. We have previously shown that the double plant homeodomain finger (DPF) of MORF is capable of binding to acetylated histone H3. Here we demonstrate that the DPF of MORF recognizes many newly identified acylation marks. The mass spectrometry study provides comprehensive analysis of H3K14 acylation states in vitro and in vivo. The crystal structure of the MORF DPF-H3K14butyryl complex offers insight into the selectivity of this reader toward lipophilic acyllysine substrates. Together, our findings support the mechanism by which the acetyltransferase MORF promotes spreading of histone acylation.
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Brianna J
authors.initials: BJ
authors.lastname: Klein
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Johayra
authors.initials: J
authors.lastname: Simithy
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: JaeWoo
authors.initials: J
authors.lastname: Ahn
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: Laval University Cancer Research Center, CHU de Québec-UL Research Center-Oncology Axis, Quebec City, QC G1R 3S3, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Côté
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Shi
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: bgarci@mail.med.upenn.edu.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
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: D000107:Acetylation; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D013058:Mass Spectrometry; D011485:Protein Binding; D000072417:Protein Domains; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D051548:Histone Acetyltransferases; C487137:KAT6B protein, human; D008239:Lysine
keywords: DPF; MORF; PTM; double PHD finger; epigenetic; histone binding; lysine acylation