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Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells

Kousuke Uranishi, Masataka Hirasaki, Yuka Kitamura, Yosuke Mizuno, Masazumi Nishimoto, Ayumu Suzuki, Akihiko Okuda
doi: https://doi.org/10.1101/2020.07.21.215079
Kousuke Uranishi
1Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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Masataka Hirasaki
2Department of Clinical Cancer Genomics, International Medical Center, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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Yuka Kitamura
1Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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Yosuke Mizuno
3Biomedical Research Center, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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Masazumi Nishimoto
1Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
3Biomedical Research Center, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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Ayumu Suzuki
1Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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  • For correspondence: ayumu@saitama-med.ac.jp akiokuda@saitama-med.ac.jp
Akihiko Okuda
1Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1, Yamane Hidaka, Saitama 350-1241, Japan
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  • For correspondence: ayumu@saitama-med.ac.jp akiokuda@saitama-med.ac.jp
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SUMMARY

Mouse embryonic stem cells (ESCs) have high potential for meiotic entry, like germ cells. Although the physiological meaning of this potential is not known, it is certain that a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively, in which MGA has important roles in DNA binding as well as in constructing the complex as a scaffolding component. As a salient feature, MGA bears two distinct DNA-binding domains termed bHLHZ and T-box. However, how these features contribute to the functions of PRC1.6, particularly in the repression of meiotic genes, remains largely obscure. Here, we demonstrated that both DNA binding domains of Mga repress distinct sets of genes in murine ESCs, and substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that both DNA binding domains of Mga, in particular bHLHZ, are crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry in collaboration with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 22, 2020.
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Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells
Kousuke Uranishi, Masataka Hirasaki, Yuka Kitamura, Yosuke Mizuno, Masazumi Nishimoto, Ayumu Suzuki, Akihiko Okuda
bioRxiv 2020.07.21.215079; doi: https://doi.org/10.1101/2020.07.21.215079
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Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells
Kousuke Uranishi, Masataka Hirasaki, Yuka Kitamura, Yosuke Mizuno, Masazumi Nishimoto, Ayumu Suzuki, Akihiko Okuda
bioRxiv 2020.07.21.215079; doi: https://doi.org/10.1101/2020.07.21.215079

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