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SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline

Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent pro...

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Autores principales: Ito, Toshiaki, Osada, Atsuki, Ohta, Masami, Yokota, Kana, Nishiyama, Akira, Niikura, Yuichi, Tamura, Tomohiko, Sekita, Yoichi, Kimura, Tohru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674328/
https://www.ncbi.nlm.nih.gov/pubmed/34912016
http://dx.doi.org/10.1038/s41598-021-03538-8
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author Ito, Toshiaki
Osada, Atsuki
Ohta, Masami
Yokota, Kana
Nishiyama, Akira
Niikura, Yuichi
Tamura, Tomohiko
Sekita, Yoichi
Kimura, Tohru
author_facet Ito, Toshiaki
Osada, Atsuki
Ohta, Masami
Yokota, Kana
Nishiyama, Akira
Niikura, Yuichi
Tamura, Tomohiko
Sekita, Yoichi
Kimura, Tohru
author_sort Ito, Toshiaki
collection PubMed
description Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent prospermatogonia, respectively. Here, we show that the transition from PGCs to sex-specific germ cells was abrogated in conditional knockout mice carrying a null mutation of Smarcb1 (also known as Snf5) gene, which encodes a core subunit of the SWI/SNF chromatin remodeling complex. In female mutant mice, failure to upregulate meiosis-related genes resulted in impaired meiotic entry and progression, including defects in synapsis formation and DNA double strand break repair. Mutant male mice exhibited delayed mitotic arrest and DNA hypomethylation in retrotransposons and imprinted genes, resulting from aberrant expression of genes related to growth and de novo DNA methylation. Collectively, our results demonstrate that the SWI/SNF complex is required for transcriptional reprogramming in the initiation of sex-dependent differentiation of germ cells.
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spelling pubmed-86743282021-12-20 SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline Ito, Toshiaki Osada, Atsuki Ohta, Masami Yokota, Kana Nishiyama, Akira Niikura, Yuichi Tamura, Tomohiko Sekita, Yoichi Kimura, Tohru Sci Rep Article Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent prospermatogonia, respectively. Here, we show that the transition from PGCs to sex-specific germ cells was abrogated in conditional knockout mice carrying a null mutation of Smarcb1 (also known as Snf5) gene, which encodes a core subunit of the SWI/SNF chromatin remodeling complex. In female mutant mice, failure to upregulate meiosis-related genes resulted in impaired meiotic entry and progression, including defects in synapsis formation and DNA double strand break repair. Mutant male mice exhibited delayed mitotic arrest and DNA hypomethylation in retrotransposons and imprinted genes, resulting from aberrant expression of genes related to growth and de novo DNA methylation. Collectively, our results demonstrate that the SWI/SNF complex is required for transcriptional reprogramming in the initiation of sex-dependent differentiation of germ cells. Nature Publishing Group UK 2021-12-15 /pmc/articles/PMC8674328/ /pubmed/34912016 http://dx.doi.org/10.1038/s41598-021-03538-8 Text en © The Author(s) 2021 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ito, Toshiaki
Osada, Atsuki
Ohta, Masami
Yokota, Kana
Nishiyama, Akira
Niikura, Yuichi
Tamura, Tomohiko
Sekita, Yoichi
Kimura, Tohru
SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
title SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
title_full SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
title_fullStr SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
title_full_unstemmed SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
title_short SWI/SNF chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
title_sort swi/snf chromatin remodeling complex is required for initiation of sex-dependent differentiation in mouse germline
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674328/
https://www.ncbi.nlm.nih.gov/pubmed/34912016
http://dx.doi.org/10.1038/s41598-021-03538-8
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