Zfp281 orchestrates interconversion of pluripotent states by engaging Ehmt1 and Zic2

被引:19
作者
Mayer, Daniela [1 ,2 ]
Stadler, Michael B. [1 ,3 ]
Rittirsch, Melanie [1 ]
Hess, Daniel [1 ]
Lukonin, Ilya [1 ,2 ]
Winzi, Maria [4 ]
Smith, Austin [5 ,6 ]
Buchholz, Frank [4 ]
Betschinger, Joerg [1 ]
机构
[1] Friedrich Miescher Inst Biomed Res, Basel, Switzerland
[2] Univ Basel, Fac Sci, Basel, Switzerland
[3] Swiss Inst Bioinformat, Basel, Switzerland
[4] Tech Univ Dresden, Med Fac Carl Gustav Carus, UCC, Med Syst Biol, Dresden, Germany
[5] Univ Cambridge, Wellcome MRC Cambridge Stem Cell Inst, Cambridge, England
[6] Univ Cambridge, Dept Biochem, Cambridge, England
基金
英国医学研究理事会;
关键词
cell state transition; cellular plasticity; differentiation; pluripotency; reprogramming; EPIBLAST STEM-CELLS; DNA METHYLATION; GROUND-STATE; HISTONE METHYLTRANSFERASES; MAINTAINS PLURIPOTENCY; NAIVE PLURIPOTENCY; RNAI SCREEN; MOUSE; G9A; TRANSCRIPTION;
D O I
10.15252/embj.2019102591
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Developmental cell fate specification is a unidirectional process that can be reverted in response to injury or experimental reprogramming. Whether differentiation and de-differentiation trajectories intersect mechanistically is unclear. Here, we performed comparative screening in lineage-related mouse naive embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), and identified the constitutively expressed zinc finger transcription factor (TF) Zfp281 as a bidirectional regulator of cell state interconversion. We showed that subtle chromatin binding changes in differentiated cells translate into activation of the histone H3 lysine 9 (H3K9) methyltransferase Ehmt1 and stabilization of the zinc finger TF Zic2 at enhancers and promoters. Genetic gain-of-function and loss-of-function experiments confirmed a critical role of Ehmt1 and Zic2 downstream of Zfp281 both in driving exit from the ESC state and in restricting reprogramming of EpiSCs. Our study reveals that cell type-invariant chromatin association of Zfp281 provides an interaction platform for remodeling the cis-regulatory network underlying cellular plasticity.
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页数:22
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共 96 条
[1]   Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition [J].
Acampora, Dario ;
Di Giovannantonio, Luca G. ;
Simeone, Antonio .
DEVELOPMENT, 2013, 140 (01) :43-55
[2]   Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease [J].
Acloque, Herve ;
Adams, Meghan S. ;
Fishwick, Katherine ;
Bronner-Fraser, Marianne ;
Angela Nieto, M. .
JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (06) :1438-1449
[3]   Nascent Induced Pluripotent Stem Cells Efficiently Generate Entirely iPSC-Derived Mice while Expressing Differentiation-Associated Genes [J].
Amlani, Bhishma ;
Liu, Yiyuan ;
Chen, Taotao ;
Ee, Ly-Sha ;
Lopez, Peter ;
Heguy, Adriana ;
Apostolou, Effie ;
Kim, Sang Yong ;
Stadtfeld, Matthias .
CELL REPORTS, 2018, 22 (04) :876-884
[4]   Derivation of hypermethylated pluripotent embryonic stem cells with high potency [J].
Bao, Siqin ;
Tang, Walfred W. C. ;
Wu, Baojiang ;
Kim, Shinseog ;
Li, Jingyun ;
Li, Lin ;
Kobayashi, Toshihiro ;
Lee, Caroline ;
Chen, Yanglin ;
Wei, Mengyi ;
Li, Shudong ;
Dietmann, Sabine ;
Tang, Fuchou ;
Li, Xihe ;
Surani, M. Azim .
CELL RESEARCH, 2018, 28 (01) :22-34
[5]   Exit from Pluripotency Is Gated by Intracellular Redistribution of the bHLH Transcription Factor Tfe3 [J].
Betschinger, Joerg ;
Nichols, Jennifer ;
Dietmann, Sabine ;
Corrin, Philip D. ;
Paddison, Patrick J. ;
Smith, Austin .
CELL, 2013, 153 (02) :335-347
[6]   Lineage-Specific Profiling Delineates the Emergence and Progression of Naive Pluripotency in Mammalian Embryogenesis [J].
Boroviak, Thorsten ;
Loos, Remco ;
Lombard, Patrick ;
Okahara, Junko ;
Behr, Ruediger ;
Sasaki, Erika ;
Nichols, Jennifer ;
Smith, Austin ;
Bertone, Paul .
DEVELOPMENTAL CELL, 2015, 35 (03) :366-382
[7]   The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification [J].
Boroviak, Thorsten ;
Loos, Remco ;
Bertone, Paul ;
Smith, Austin ;
Nichols, Jennifer .
NATURE CELL BIOLOGY, 2014, 16 (06) :513-+
[8]   Derivation of pluripotent epiblast stem cells from mammalian embryos [J].
Brons, I. Gabrielle M. ;
Smithers, Lucy E. ;
Trotter, Matthew W. B. ;
Rugg-Gunn, Peter ;
Sun, Bowen ;
de Sousa Lopes, Susana M. Chuva ;
Howlett, Sarah K. ;
Clarkson, Amanda ;
Ahrlund-Richter, Lars ;
Pedersen, Roger A. ;
Vallier, Ludovic .
NATURE, 2007, 448 (7150) :191-U7
[9]   Regulation of Pluripotency and Cellular Reprogramming by the Ubiquitin-Proteasome System [J].
Buckley, Shannon M. ;
Aranda-Orgilles, Beatriz ;
Strikoudis, Alexandros ;
Apostolou, Effie ;
Loizou, Evangelia ;
Moran-Crusio, Kelly ;
Farnsworth, Charles L. ;
Koller, Antonius A. ;
Dasgupta, Ramanuj ;
Silva, Jeffrey C. ;
Stadtfeld, Matthias ;
Hochedlinger, Konrad ;
Chen, Emily I. ;
Aifantis, Iannis .
CELL STEM CELL, 2012, 11 (06) :783-798
[10]   Reorganization of Enhancer Patterns in Transition from Naive to Primed Pluripotency [J].
Buecker, Christa ;
Srinivasan, Rajini ;
Wu, Zhixiang ;
Calo, Eliezer ;
Acampora, Dario ;
Faial, Tiago ;
Simeone, Antonio ;
Tan, Minjia ;
Swigut, Tomasz ;
Wysocka, Joanna .
CELL STEM CELL, 2014, 14 (06) :838-853