title: PHF20 Readers Link Methylation of Histone H3K4 and p53 with H4K16 Acetylation.
abstract: PHF20 is a core component of the lysine acetyltransferase complex MOF (male absent on the first)-NSL (non-specific lethal) that generates the major epigenetic mark H4K16ac and is necessary for transcriptional regulation and DNA repair. The role of PHF20 in the complex remains elusive. Here, we report on functional coupling between methylation readers in PHF20. We show that the plant homeodomain (PHD) finger of PHF20 recognizes dimethylated lysine 4 of histone H3 (H3K4me2) and represents an example of a native reader that selects for this modification. Biochemical and structural analyses help to explain this selectivity and the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a unique PHF20-mediated link between MOF histone acetyltransferase (HAT), p53, and H3K4me2, and suggest a model for rapid spreading of H4K16ac-enriched open chromatin.
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: Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Faculty of Medicine, Ludwig Maximilian University of Munich, Munich 80336, Germany.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Cui
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: Chao
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Botuyan
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: Kevin
authors.initials: K
authors.lastname: Lin
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: Yue
authors.initials: Y
authors.lastname: Lu
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 General, Visceral and Tumor Surgery, University Clinic Cologne, Cologne 50931, Germany.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Faculty of Medicine, Ludwig Maximilian University of Munich, Munich 80336, Germany; Department of General, Visceral and Tumor Surgery, University Clinic Cologne, Cologne 50931, Germany.
authors.forename: Christiane J
authors.initials: CJ
authors.lastname: Bruns
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: mer.georges@mayo.edu.
authors.forename: Georges
authors.initials: G
authors.lastname: Mer
authors.affiliation: Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: xbshi@mdanderson.org.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Shi
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; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D018698:Glutamic Acid / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D000072417:Protein Domains; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006657:Histones; C440091:PHF20 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D001224:Aspartic Acid; D018698:Glutamic Acid; D008239:Lysine
keywords: MOF; PHD finger; PHF20; Tudor; chromatin; histone acetylation; histone methylation; p53