PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex

被引：43

作者：

Link, Stephanie ^{[1
,2
]}

Spitzer, Ramona M. M. ^{[1
,2
]}

Sana, Maryam ^{[3
]}

Torrado, Mario ^{[3
]}

Voelker-Albert, Moritz C. ^{[1
]}

Keilhauer, Eva C. ^{[4
,10
]}

Burgold, Thomas ^{[5
,6
,11
]}

Puenzeler, Sebastian ^{[1
,12
]}

Low, Jason K. K. ^{[3
]}

Lindstroem, Ida ^{[3
]}

Nist, Andrea ^{[7
]}

Regnard, Catherine ^{[1
]}

Stiewe, Thorsten ^{[7
,8
]}

Hendrich, Brian ^{[5
,6
]}

Imhof, Axel ^{[1
,9
]}

Mann, Matthias ^{[4
,9
]}

Mackay, Joel P. ^{[3
]}

Bartkuhn, Marek ^{[2
]}

Hake, Sandra B. ^{[2
,9
]}

机构：

[1] Ludwig Maximilians Univ Munchen, BioMed Ctr BMC, Dept Mol Biol, D-82152 Planegg Martinsried, Germany

[2] Justus Liebig Univ Giessen, Inst Genet, D-35392 Giessen, Germany

[3] Univ Sydney, Sch Life & Environm Sci, Sydney, NSW 2006, Australia

[4] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[5] Univ Cambridge, Wellcome Trust MRC Stem Cell Inst, Cambridge CB2 1QR, England

[6] Univ Cambridge, Dept Biochem, Cambridge CB2 1QR, England

[7] Philipps Univ Marburg, Genom Core Facil, D-35043 Marburg, Germany

[8] Philipps Univ Marburg, Inst Mol Oncol, D-35043 Marburg, Germany

[9] CIPSM, D-81377 Munich, Germany

[10] Coriolis Pharma, Fraunhoferstr 18B, D-82152 Planegg, Germany

[11] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England

[12] Coparion GmbH & Co KG, Charles de Gaulle Pl 1d, D-50679 Cologne, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

GENE-EXPRESSION; DEACETYLASE COMPLEX; STATE DISCOVERY; TRANSCRIPTION; PLURIPOTENCY; METHYLATION; BIOCONDUCTOR; ANNOTATION; LYSINE-36; COMPONENT;

D O I：

10.1038/s41467-018-06665-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A. Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.

引用

页数：16

共 67 条

[41] Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation [J].

Puenzeler, Sebastian ;

Link, Stephanie ;

Wagner, Gabriele ;

Keilhauer, Eva C. ;

Kronbeck, Nina ;

Spitzer, Ramona M. M. ;

Leidescher, Susanne ;

Markaki, Yolanda ;

Mentele, Edith ;

Regnard, Catherine ;

Schneider, Katrin ;

Takahashi, Daisuke ;

Kusakabe, Masayuki ;

Vardabasso, Chiara ;

Zink, Lisa M. ;

Straub, Tobias ;

Bernstein, Emily ;

Harata, Masahiko ;

Leonhardt, Heinrich ;

Mann, Matthias ;

Rupp, Ralph A. W. ;

Hake, Sandra B. .

EMBO JOURNAL, 2017, 36 (15) :2263-2279

[42] The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds [J].

Qiu, C ;

Sawada, K ;

Zhang, X ;

Cheng, XD .

NATURE STRUCTURAL BIOLOGY, 2002, 9 (03) :217-224

[43] deepTools: a flexible platform for exploring deep-sequencing data [J].

Ramirez, Fidel ;

Duendar, Friederike ;

Diehl, Sarah ;

Gruening, Bjoern A. ;

Manke, Thomas .

NUCLEIC ACIDS RESEARCH, 2014, 42 (W1) :W187-W191

[44] Transcriptional repressors: multifaceted regulators of gene expression [J].

Reynolds, Nicola ;

O'Shaughnessy, Aoife ;

Hendrich, Brian .

DEVELOPMENT, 2013, 140 (03) :505-512

[45] NuRD Suppresses Pluripotency Gene Expression to Promote Transcriptional Heterogeneity and Lineage Commitment [J].

Reynolds, Nicola ;

Latos, Paulina ;

Hynes-Allen, Antony ;

Loos, Remco ;

Leaford, Donna ;

O'Shaughnessy, Aoife ;

Mosaku, Olukunbi ;

Signolet, Jason ;

Brennecke, Philip ;

Kalkan, Tuezer ;

Costello, Ita ;

Humphreys, Peter ;

Mansfield, William ;

Nakagawa, Kentaro ;

Strouboulis, John ;

Behrens, Axel ;

Bertone, Paul ;

Hendrich, Brian .

CELL STEM CELL, 2012, 10 (05) :583-594

[46] NuRD-mediated deacetylation of H3K27 facilitates recruitment of Polycomb Repressive Complex 2 to direct gene repression [J].

Reynolds, Nicola ;

Salmon-Divon, Mali ;

Dvinge, Heidi ;

Hynes-Allen, Antony ;

Balasooriya, Gayan ;

Leaford, Donna ;

Behrens, Axel ;

Bertone, Paul ;

Hendrich, Brian .

EMBO JOURNAL, 2012, 31 (03) :593-605

[47] PWWP domains and their modes of sensing DNA and histone methylated lysines [J].

Rona G.B. ;

Eleutherio E.C.A. ;

Pinheiro A.S. .

Biophysical Reviews, 2016, 8 (1) :63-74

[48] Histone H2A.Z regulates transcription and is partially redundant with nucleosome remodeling complexes [J].

Santisteban, MS ;

Kalashnikova, T ;

Smith, MM .

CELL, 2000, 103 (03) :411-422

[49]

Schnitzler G.R, 2001, CURR PROTOC MOL BIOL

[50] CDK2AP1/DOC-1 is a bona fide subunit of the Mi-2/NuRD complex [J].

Spruijt, Cornelia G. ;

Bartels, Stefanie J. J. ;

Brinkman, Arie B. ;

Tjeertes, Jorrit V. ;

Poser, Ina ;

Stunnenberg, Hendrik G. ;

Vermeulen, Michiel .

MOLECULAR BIOSYSTEMS, 2010, 6 (09) :1700-1706

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