title: PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3.
abstract: PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA PolII. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Ho-Ryun
authors.initials: HR
authors.lastname: Chung
authors.affiliation: Structural Genomics Consortium, Toronto, Canada.
authors.forename: Chao
authors.identifier: 0000-0003-0444-7080
authors.initials: C
authors.lastname: Xu
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Alisa
authors.initials: A
authors.lastname: Fuchs
authors.affiliation: Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mund
authors.affiliation: Centre for Genomic Regulation, Barcelona, Spain.
authors.forename: Martin
authors.identifier: 0000-0003-1650-533X
authors.initials: M
authors.lastname: Lange
authors.affiliation: Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Hannah
authors.initials: H
authors.lastname: Staege
authors.affiliation: Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schubert
authors.affiliation: Structural Genomics Consortium, Toronto, Canada.
authors.forename: Chuanbing
authors.initials: C
authors.lastname: Bian
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Ilona
authors.initials: I
authors.lastname: Dunkel
authors.affiliation: Adolf-Butenandt-Institute and Center for Integrated Protein Science, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Eberharter
authors.affiliation: Adolf-Butenandt-Institute and Center for Integrated Protein Science, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Regnard
authors.affiliation: Adolf-Butenandt-Institute and Center for Integrated Protein Science, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Klinker
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Meierhofer
authors.affiliation: Centre for Genomic Regulation, Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Luca
authors.identifier: 0000-0003-3194-8892
authors.initials: L
authors.lastname: Cozzuto
authors.affiliation: Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Winterpacht
authors.affiliation: Centre for Genomic Regulation, Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats, Pg. Lluis Companys, Barcelona, Spain.
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
authors.affiliation: Structural Genomics Consortium, Toronto, Canada.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Min
authors.affiliation: Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Will
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.|Heinrich-Pette-Institute - Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Sarah
authors.identifier: 0000-0003-4997-4749
authors.initials: S
authors.lastname: Kinkley
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D011485:Protein Binding; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; C503048:PHF13 protein, human; D014157:Transcription Factors; D004247:DNA
keywords: PHD domain; PRC2; RNA polymerase II; biophysics; chromosomes; genes; human; molecular reader and effector; mouse; structural biology; transcriptional regulator