PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

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 local...

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Autores: Chung, Ho-Ryun, Xu, Chao, Fuchs, Alisa, Mund, Andreas, Lange, Martin, Staege, Hannah, Schubert, Tobias, Bian, Chuanbing, Dunkel, Ilona, Eberharter, Anton, Regnard, Catherine, Klinker, Henrike, Meierhofer, David, Cozzuto, Luca, Winterpacht, Andreas, Di Croce, Luciano, Min, Jinrong, Will, Hans, Kinkley, Sarah
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2016
País:España
Recursos:Universitat Pompeu Fabra
Repositório:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/27902
Acesso em linha:http://hdl.handle.net/10230/27902
http://dx.doi.org/10.7554/eLife.10607
Access Level:Acceso aberto
Palavra-chave:Citologia
Cromatina
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spelling PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3Chung, Ho-RyunXu, ChaoFuchs, AlisaMund, AndreasLange, MartinStaege, HannahSchubert, TobiasBian, ChuanbingDunkel, IlonaEberharter, AntonRegnard, CatherineKlinker, HenrikeMeierhofer, DavidCozzuto, LucaWinterpacht, AndreasDi Croce, LucianoMin, JinrongWill, HansKinkley, SarahCitologiaCromatinaPHF13 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.This work was mainly funded by a grant from the Deutsche Krebshilfe #10-2243-Wi4 and by the Max Planck Society. The Heinrich Pette Institute is supported by the Freie und Hansestadt Hamburg and the German Federal Ministry of Health and Social Security. The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck & Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, São Paulo Research Foundation-FAPESP, Takeda, and the Wellcome Trust (to JM).eLife201720172016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/27902http://dx.doi.org/10.7554/eLife.10607reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésElife. 2016; 5: e10607info:eu-repo/grantAgreement/EC/FP7/115766(c) Copyright Chung et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/279022026-06-12T07:21:37Z
dc.title.none.fl_str_mv PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
title PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
spellingShingle PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
Chung, Ho-Ryun
Citologia
Cromatina
title_short PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
title_full PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
title_fullStr PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
title_full_unstemmed PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
title_sort PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3
dc.creator.none.fl_str_mv Chung, Ho-Ryun
Xu, Chao
Fuchs, Alisa
Mund, Andreas
Lange, Martin
Staege, Hannah
Schubert, Tobias
Bian, Chuanbing
Dunkel, Ilona
Eberharter, Anton
Regnard, Catherine
Klinker, Henrike
Meierhofer, David
Cozzuto, Luca
Winterpacht, Andreas
Di Croce, Luciano
Min, Jinrong
Will, Hans
Kinkley, Sarah
author Chung, Ho-Ryun
author_facet Chung, Ho-Ryun
Xu, Chao
Fuchs, Alisa
Mund, Andreas
Lange, Martin
Staege, Hannah
Schubert, Tobias
Bian, Chuanbing
Dunkel, Ilona
Eberharter, Anton
Regnard, Catherine
Klinker, Henrike
Meierhofer, David
Cozzuto, Luca
Winterpacht, Andreas
Di Croce, Luciano
Min, Jinrong
Will, Hans
Kinkley, Sarah
author_role author
author2 Xu, Chao
Fuchs, Alisa
Mund, Andreas
Lange, Martin
Staege, Hannah
Schubert, Tobias
Bian, Chuanbing
Dunkel, Ilona
Eberharter, Anton
Regnard, Catherine
Klinker, Henrike
Meierhofer, David
Cozzuto, Luca
Winterpacht, Andreas
Di Croce, Luciano
Min, Jinrong
Will, Hans
Kinkley, Sarah
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Citologia
Cromatina
topic Citologia
Cromatina
description 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.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/27902
http://dx.doi.org/10.7554/eLife.10607
url http://hdl.handle.net/10230/27902
http://dx.doi.org/10.7554/eLife.10607
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Elife. 2016; 5: e10607
info:eu-repo/grantAgreement/EC/FP7/115766
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv eLife
publisher.none.fl_str_mv eLife
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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