Rcor2 Is Required for Somatic Differentiation and Represses Germline Cell Fate

被引：2

作者：

Pei, Lijuan ^{[1
]}

Zhang, Hongjie ^{[1
]}

Zhang, Meihui ^{[1
]}

Wang, Yixuan ^{[2
]}

Wei, Ke ^{[1
]}

机构：

[1] Tongji Univ, Shanghai Inst Stem Cell Res & Clin Translat, Shanghai Key Lab Signaling & Dis Res,Sch Life Sci, Inst Regenerat Med,Shanghai East Hosp,Frontier Sc, Shanghai 200092, Peoples R China

[2] Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Key Lab Signaling & Dis Res,Minist Educ, Clin & Translat Res Ctr,Sch Life Sci & Technol,Fr, Shanghai 200092, Peoples R China

来源：

STEM CELLS INTERNATIONAL | 2022年 / 2022卷

基金：

中国国家自然科学基金;

关键词：

REST; COREST; SPECIFICATION; DYNAMICS; COMPLEX;

D O I：

10.1155/2022/5283615

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Rcor2, the corepressor 2 of REST, a transcriptional repressor, is predominantly expressed in embryonic stem cells (ESCs) and plays a major role in regulating ESC pluripotency and neurogenesis. The function of Rcor2 in development of other germ layers is yet unclear. We utilized a Rcor2(-/-) mouse embryonic stem cell (mESC) line to investigate the role of Rcor2 in mESC differentiation. Rcor2(-/-) mESC shows reduced proliferation and severely compromised capacity to differentiate to all three germ layers. In contrast, Rcor2 knockout promotes primordial germ cells (PGCs) specific gene expression and possibly PGC formation. Mechanistically, we revealed that Rcor2 inhibits expression of genes required for PGC development, such as Dppa3 and Dazl, by associating to their promoters and enhancing local suppressive H3K9me3 modifications. Our results suggest that Rcor2 plays an important role in somatic cell fate determination by suppressing PGC differentiation through regulating epigenetic modifications of PGC specific genes.

引用

页数：11

共 27 条

[1] REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis [J].

Ballas, N ;

Grunseich, C ;

Lu, DD ;

Speh, JC ;

Mandel, G .

CELL, 2005, 121 (04) :645-657

[2] H3K9me3-Dependent Heterochromatin: Barrier to Cell Fate Changes [J].

Becker, Justin S. ;

Nicetto, Dario ;

Zaret, Kenneth S. .

TRENDS IN GENETICS, 2016, 32 (01) :29-41

[3] The Encyclopedia of DNA elements (ENCODE): data portal update [J].

Davis, Carrie A. ;

Hitz, Benjamin C. ;

Sloan, Cricket A. ;

Chan, Esther T. ;

Davidson, Jean M. ;

Gabdank, Idan ;

Hilton, Jason A. ;

Jain, Kriti ;

Baymuradov, Ulugbek K. ;

Narayanan, Aditi K. ;

Onate, Kathrina C. ;

Graham, Keenan ;

Miyasato, Stuart R. ;

Dreszer, Timothy R. ;

Strattan, J. Seth ;

Jolanki, Otto ;

Tanaka, Forrest Y. ;

Cherry, J. Michael .

NUCLEIC ACIDS RESEARCH, 2018, 46 (D1) :D794-D801

[4] Lysine-Specific Demethylase 1 Regulates the Embryonic Transcriptome and CoREST Stability [J].

Foster, Charles T. ;

Dovey, Oliver M. ;

Lezina, Larissa ;

Luo, Jin Li ;

Gant, Timothy W. ;

Barlev, Nick ;

Bradley, Allan ;

Cowley, Shaun M. .

MOLECULAR AND CELLULAR BIOLOGY, 2010, 30 (20) :4851-4863

[5] Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine [J].

Hackett, Jamie A. ;

Sengupta, Roopsha ;

Zylicz, Jan J. ;

Murakami, Kazuhiro ;

Lee, Caroline ;

Down, Thomas A. ;

Surani, M. Azim .

SCIENCE, 2013, 339 (6118) :448-452

[6] Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline [J].

Hackett, Jamie A. ;

Reddington, James P. ;

Nestor, Colm E. ;

Dunican, Donncha S. ;

Branco, Miguel R. ;

Reichmann, Judith ;

Reik, Wolf ;

Surani, M. Azim ;

Adams, Ian R. ;

Meehan, Richard R. .

DEVELOPMENT, 2012, 139 (19) :3623-3632

[7] Epigenetic reprogramming in mouse primordial germ cells [J].

Hajkova, P ;

Erhardt, S ;

Lane, N ;

Haaf, T ;

El-Maarri, O ;

Reik, W ;

Walter, J ;

Surani, MA .

MECHANISMS OF DEVELOPMENT, 2002, 117 (1-2) :15-23

[8] Offspring from Oocytes Derived from in Vitro Primordial Germ Cell-like Cells in Mice [J].

Hayashi, Katsuhiko ;

Ogushi, Sugako ;

Kurimoto, Kazuki ;

Shimamoto, So ;

Ohta, Hiroshi ;

Saitou, Mitinori .

SCIENCE, 2012, 338 (6109) :971-975

[9] Reconstitution of the Mouse Germ Cell Specification Pathway in Culture by Pluripotent Stem Cells [J].

Hayashi, Katsuhiko ;

Ohta, Hiroshi ;

Kurimoto, Kazuki ;

Aramaki, Shinya ;

Saitou, Mitinori .

CELL, 2011, 146 (04) :519-532

[10] Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte [J].

Hill, Peter W. S. ;

Leitch, Harry G. ;

Requena, Cristina E. ;

Sun, Zhiyi ;

Amouroux, Rachel ;

Roman-Trufero, Monica ;

Borkowska, Malgorzata ;

Terragni, Jolyon ;

Vaisvila, Romualdas ;

Linnett, Sarah ;

Bagci, Hakan ;

Dharmalingham, Gopuraja ;

Haberle, Vanja ;

Lenhard, Boris ;

Zheng, Yu ;

Pradhan, Sriharsa ;

Hajkova, Petra .

NATURE, 2018, 555 (7696) :392-+

← 1 2 3 →