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

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

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

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dc.contributor.author Chung, Ho-Ryunca
dc.contributor.author Xu, Chaoca
dc.contributor.author Fuchs, Alisaca
dc.contributor.author Mund, Andreasca
dc.contributor.author Lange, Martinca
dc.contributor.author Staege, Hannahca
dc.contributor.author Schubert, Tobiasca
dc.contributor.author Bian, Chuanbingca
dc.contributor.author Dunkel, Ilonaca
dc.contributor.author Eberharter, Antonca
dc.contributor.author Regnard, Catherineca
dc.contributor.author Klinker, Henrikeca
dc.contributor.author Meierhofer, Davidca
dc.contributor.author Cozzuto, Lucaca
dc.contributor.author Winterpacht, Andreasca
dc.contributor.author Di Croce, Lucianoca
dc.contributor.author Min, Jinrongca
dc.contributor.author Will, Hansca
dc.contributor.author Kinkley, Sarahca
dc.date.accessioned 2017-01-16T12:00:12Z
dc.date.available 2017-01-16T12:00:12Z
dc.date.issued 2016ca
dc.description.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.
dc.description.sponsorship 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).
dc.format.mimetype application/pdfca
dc.identifier.citation Chung H-R, Xu C, Fuchs A, Mund A, Lange M, Staege H, Schubert T, Bian C, Dunkel I, Eberharter A, Regnard C, Klinker H, Meierhofer D, Cozzuto L, Winterpacht A, Di Croce L, Min J, Will H, Kinkley S. PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3. Elife. 2016; 5: e10607. DOI: http://dx.doi.org/10.7554/eLife.10607ca
dc.identifier.doi http://dx.doi.org/10.7554/eLife.10607
dc.identifier.issn 2050-084Xca
dc.identifier.uri http://hdl.handle.net/10230/27902
dc.language.iso engca
dc.publisher eLifeca
dc.relation.ispartof Elife. 2016; 5: e10607
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115766
dc.rights (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.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Citologia
dc.subject.other Cromatina
dc.title PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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