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Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin

Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present a novel mouse model of paternal ep...

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Autores principales: Sakashita, Akihiko, Ooga, Masatoshi, Otsuka, Kai, Maezawa, So, Takeuchi, Chikara, Wakayama, Sayaka, Wakayama, Teruhiko, Namekawa, Satoshi H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359620/
https://www.ncbi.nlm.nih.gov/pubmed/37283086
http://dx.doi.org/10.1093/nar/gkad479
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author Sakashita, Akihiko
Ooga, Masatoshi
Otsuka, Kai
Maezawa, So
Takeuchi, Chikara
Wakayama, Sayaka
Wakayama, Teruhiko
Namekawa, Satoshi H
author_facet Sakashita, Akihiko
Ooga, Masatoshi
Otsuka, Kai
Maezawa, So
Takeuchi, Chikara
Wakayama, Sayaka
Wakayama, Teruhiko
Namekawa, Satoshi H
author_sort Sakashita, Akihiko
collection PubMed
description Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present a novel mouse model of paternal epigenetic inheritance, in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology using testicular sperm, we rescued infertility of mice missing Polycomb protein SCML2, which regulates germline gene expression by establishing H3K27me3 on bivalent promoters with other active marks H3K4me2/3. We profiled epigenomic states (H3K27me3 and H3K4me3) of testicular sperm and epididymal sperm, demonstrating that the epididymal pattern of the sperm epigenome is already established in testicular sperm and that SCML2 is required for this process. In F1 males of X-linked Scml2-knockout mice, which have a wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in F0 sperm. Further, dysregulation of gene expression was observed in the mutant-derived wild-type F1 preimplantation embryos. Together, we present functional evidence that the classic epigenetic regulator Polycomb mediates paternal epigenetic inheritance through sperm chromatin.
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spelling pubmed-103596202023-07-22 Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin Sakashita, Akihiko Ooga, Masatoshi Otsuka, Kai Maezawa, So Takeuchi, Chikara Wakayama, Sayaka Wakayama, Teruhiko Namekawa, Satoshi H Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Sperm chromatin retains small amounts of histones, and chromatin states of sperm mirror gene expression programs of the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through sperm chromatin. Here, we present a novel mouse model of paternal epigenetic inheritance, in which deposition of Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 is attenuated in the paternal germline. By applying modified methods of assisted reproductive technology using testicular sperm, we rescued infertility of mice missing Polycomb protein SCML2, which regulates germline gene expression by establishing H3K27me3 on bivalent promoters with other active marks H3K4me2/3. We profiled epigenomic states (H3K27me3 and H3K4me3) of testicular sperm and epididymal sperm, demonstrating that the epididymal pattern of the sperm epigenome is already established in testicular sperm and that SCML2 is required for this process. In F1 males of X-linked Scml2-knockout mice, which have a wild-type genotype, gene expression is dysregulated in the male germline during spermiogenesis. These dysregulated genes are targets of SCML2-mediated H3K27me3 in F0 sperm. Further, dysregulation of gene expression was observed in the mutant-derived wild-type F1 preimplantation embryos. Together, we present functional evidence that the classic epigenetic regulator Polycomb mediates paternal epigenetic inheritance through sperm chromatin. Oxford University Press 2023-06-07 /pmc/articles/PMC10359620/ /pubmed/37283086 http://dx.doi.org/10.1093/nar/gkad479 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Sakashita, Akihiko
Ooga, Masatoshi
Otsuka, Kai
Maezawa, So
Takeuchi, Chikara
Wakayama, Sayaka
Wakayama, Teruhiko
Namekawa, Satoshi H
Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
title Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
title_full Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
title_fullStr Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
title_full_unstemmed Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
title_short Polycomb protein SCML2 mediates paternal epigenetic inheritance through sperm chromatin
title_sort polycomb protein scml2 mediates paternal epigenetic inheritance through sperm chromatin
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359620/
https://www.ncbi.nlm.nih.gov/pubmed/37283086
http://dx.doi.org/10.1093/nar/gkad479
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