PRC1 suppresses a female gene regulatory network to ensure testicular differentiation

Gonadal sex determination and differentiation are controlled by somatic support cells of testes (Sertoli cells) and ovaries (granulosa cells). In testes, the epigenetic mechanism that maintains chromatin states responsible for suppressing female sexual differentiation remains unclear. Here, we show...

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Autores principales: Maezawa, So, Yukawa, Masashi, Hasegawa, Kazuteru, Sugiyama, Ryo, Iizuka, Mizuho, Hu, Mengwen, Sakashita, Akihiko, Vidal, Miguel, Koseki, Haruhiko, Barski, Artem, DeFalco, Tony, Namekawa, Satoshi H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403552/
https://www.ncbi.nlm.nih.gov/pubmed/37542070
http://dx.doi.org/10.1038/s41419-023-05996-6
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author Maezawa, So
Yukawa, Masashi
Hasegawa, Kazuteru
Sugiyama, Ryo
Iizuka, Mizuho
Hu, Mengwen
Sakashita, Akihiko
Vidal, Miguel
Koseki, Haruhiko
Barski, Artem
DeFalco, Tony
Namekawa, Satoshi H.
author_facet Maezawa, So
Yukawa, Masashi
Hasegawa, Kazuteru
Sugiyama, Ryo
Iizuka, Mizuho
Hu, Mengwen
Sakashita, Akihiko
Vidal, Miguel
Koseki, Haruhiko
Barski, Artem
DeFalco, Tony
Namekawa, Satoshi H.
author_sort Maezawa, So
collection PubMed
description Gonadal sex determination and differentiation are controlled by somatic support cells of testes (Sertoli cells) and ovaries (granulosa cells). In testes, the epigenetic mechanism that maintains chromatin states responsible for suppressing female sexual differentiation remains unclear. Here, we show that Polycomb repressive complex 1 (PRC1) suppresses a female gene regulatory network in postnatal Sertoli cells. We genetically disrupted PRC1 function in embryonic Sertoli cells after sex determination, and we found that PRC1-depleted postnatal Sertoli cells exhibited defective proliferation and cell death, leading to the degeneration of adult testes. In adult Sertoli cells, PRC1 suppressed specific genes required for granulosa cells, thereby inactivating the female gene regulatory network. Chromatin regions associated with female-specific genes were marked by Polycomb-mediated repressive modifications: PRC1-mediated H2AK119ub and PRC2-mediated H3K27me3. Taken together, this study identifies a critical Polycomb-based mechanism that suppresses ovarian differentiation and maintains Sertoli cell fate in adult testes.
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spelling pubmed-104035522023-08-06 PRC1 suppresses a female gene regulatory network to ensure testicular differentiation Maezawa, So Yukawa, Masashi Hasegawa, Kazuteru Sugiyama, Ryo Iizuka, Mizuho Hu, Mengwen Sakashita, Akihiko Vidal, Miguel Koseki, Haruhiko Barski, Artem DeFalco, Tony Namekawa, Satoshi H. Cell Death Dis Article Gonadal sex determination and differentiation are controlled by somatic support cells of testes (Sertoli cells) and ovaries (granulosa cells). In testes, the epigenetic mechanism that maintains chromatin states responsible for suppressing female sexual differentiation remains unclear. Here, we show that Polycomb repressive complex 1 (PRC1) suppresses a female gene regulatory network in postnatal Sertoli cells. We genetically disrupted PRC1 function in embryonic Sertoli cells after sex determination, and we found that PRC1-depleted postnatal Sertoli cells exhibited defective proliferation and cell death, leading to the degeneration of adult testes. In adult Sertoli cells, PRC1 suppressed specific genes required for granulosa cells, thereby inactivating the female gene regulatory network. Chromatin regions associated with female-specific genes were marked by Polycomb-mediated repressive modifications: PRC1-mediated H2AK119ub and PRC2-mediated H3K27me3. Taken together, this study identifies a critical Polycomb-based mechanism that suppresses ovarian differentiation and maintains Sertoli cell fate in adult testes. Nature Publishing Group UK 2023-08-04 /pmc/articles/PMC10403552/ /pubmed/37542070 http://dx.doi.org/10.1038/s41419-023-05996-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Maezawa, So
Yukawa, Masashi
Hasegawa, Kazuteru
Sugiyama, Ryo
Iizuka, Mizuho
Hu, Mengwen
Sakashita, Akihiko
Vidal, Miguel
Koseki, Haruhiko
Barski, Artem
DeFalco, Tony
Namekawa, Satoshi H.
PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
title PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
title_full PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
title_fullStr PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
title_full_unstemmed PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
title_short PRC1 suppresses a female gene regulatory network to ensure testicular differentiation
title_sort prc1 suppresses a female gene regulatory network to ensure testicular differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403552/
https://www.ncbi.nlm.nih.gov/pubmed/37542070
http://dx.doi.org/10.1038/s41419-023-05996-6
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