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

Ho-Ryun Chung; Chao Xu; Alisa Fuchs; Andreas Mund; Martin Lange; Hannah Staege; Tobias Schubert; Chuanbing Bian; Ilona Dunkel; Anton Eberharter; Catherine Regnard; Henrike Klinker; David Meierhofer; Luca Cozzuto; Andreas Winterpacht; Luciano Di Croce; Jinrong Min; Hans Will; Sarah Kinkley

doi:10.7554/eLife.10607

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

Ho-Ryun Chung, Chao Xu, Alisa Fuchs, Andreas Mund, Martin Lange, Hannah Staege, Tobias Schubert, Chuanbing Bian, Ilona Dunkel, Anton Eberharter, Catherine Regnard, Henrike Klinker, David Meierhofer, Luca Cozzuto, Andreas Winterpacht, Luciano Di Croce, Jinrong Min, Hans Will, Sarah Kinkley

13 Citations (Scopus)

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.

Original language	English
Article number	e10607
Journal	eLife
Volume	5
ISSN	2050-084X
DOIs	https://doi.org/10.7554/eLife.10607
Publication status	Published - 25 May 2016
Externally published	Yes

Keywords

Animals
Cell Line
Chromatin/metabolism
Chromatin Immunoprecipitation
Chromatography, Gel
Crystallography, X-Ray
DNA/metabolism
DNA-Binding Proteins/chemistry
Gene Expression Regulation
Histones/metabolism
Humans
Mass Spectrometry
Mice
Protein Binding
Transcription Factors/chemistry

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10.7554/eLife.10607Licence: CC BY

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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. (2016). PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3. eLife, 5, Article e10607. https://doi.org/10.7554/eLife.10607

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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.",

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author = "Ho-Ryun Chung and Chao Xu and Alisa Fuchs and Andreas Mund and Martin Lange and Hannah Staege and Tobias Schubert and Chuanbing Bian and Ilona Dunkel and Anton Eberharter and Catherine Regnard and Henrike Klinker and David Meierhofer and Luca Cozzuto and Andreas Winterpacht and {Di Croce}, Luciano and Jinrong Min and Hans Will and Sarah Kinkley",

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T1 - PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

AU - Chung, Ho-Ryun

AU - Xu, Chao

AU - Fuchs, Alisa

AU - Mund, Andreas

AU - Lange, Martin

AU - Staege, Hannah

AU - Schubert, Tobias

AU - Bian, Chuanbing

AU - Dunkel, Ilona

AU - Eberharter, Anton

AU - Regnard, Catherine

AU - Klinker, Henrike

AU - Meierhofer, David

AU - Cozzuto, Luca

AU - Winterpacht, Andreas

AU - Di Croce, Luciano

AU - Min, Jinrong

AU - Will, Hans

AU - Kinkley, Sarah

PY - 2016/5/25

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N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - Chromatin/metabolism

KW - Chromatin Immunoprecipitation

KW - Chromatography, Gel

KW - Crystallography, X-Ray

KW - DNA/metabolism

KW - DNA-Binding Proteins/chemistry

KW - Gene Expression Regulation

KW - Histones/metabolism

KW - Humans

KW - Mass Spectrometry

KW - Mice

KW - Protein Binding

KW - Transcription Factors/chemistry

U2 - 10.7554/eLife.10607

DO - 10.7554/eLife.10607

M3 - Journal article

C2 - 27223324

SN - 2050-084X

VL - 5

JO - eLife

JF - eLife

M1 - e10607

ER -

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

Abstract

Keywords

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