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ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline
H3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and sp...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592865/ https://www.ncbi.nlm.nih.gov/pubmed/37873266 http://dx.doi.org/10.1101/2023.09.30.560314 |
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author | Alavattam, Kris G. Esparza, Jasmine M. Hu, Mengwen Shimada, Ryuki Kohrs, Anna R. Abe, Hironori Munakata, Yasuhisa Otsuka, Kai Yoshimura, Saori Kitamura, Yuka Yeh, Yu-Han Hu, Yueh-Chiang Kim, Jihye Andreassen, Paul R. Ishiguro, Kei-ichiro Namekawa, Satoshi H. |
author_facet | Alavattam, Kris G. Esparza, Jasmine M. Hu, Mengwen Shimada, Ryuki Kohrs, Anna R. Abe, Hironori Munakata, Yasuhisa Otsuka, Kai Yoshimura, Saori Kitamura, Yuka Yeh, Yu-Han Hu, Yueh-Chiang Kim, Jihye Andreassen, Paul R. Ishiguro, Kei-ichiro Namekawa, Satoshi H. |
author_sort | Alavattam, Kris G. |
collection | PubMed |
description | H3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that, in male meiosis, ATF7IP2 amasses on autosomal and X pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein’s essential roles in the maintenance of MSCI, suppression of retrotransposons, and global upregulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition. |
format | Online Article Text |
id | pubmed-10592865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-105928652023-10-24 ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline Alavattam, Kris G. Esparza, Jasmine M. Hu, Mengwen Shimada, Ryuki Kohrs, Anna R. Abe, Hironori Munakata, Yasuhisa Otsuka, Kai Yoshimura, Saori Kitamura, Yuka Yeh, Yu-Han Hu, Yueh-Chiang Kim, Jihye Andreassen, Paul R. Ishiguro, Kei-ichiro Namekawa, Satoshi H. bioRxiv Article H3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that, in male meiosis, ATF7IP2 amasses on autosomal and X pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein’s essential roles in the maintenance of MSCI, suppression of retrotransposons, and global upregulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition. Cold Spring Harbor Laboratory 2023-10-02 /pmc/articles/PMC10592865/ /pubmed/37873266 http://dx.doi.org/10.1101/2023.09.30.560314 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Alavattam, Kris G. Esparza, Jasmine M. Hu, Mengwen Shimada, Ryuki Kohrs, Anna R. Abe, Hironori Munakata, Yasuhisa Otsuka, Kai Yoshimura, Saori Kitamura, Yuka Yeh, Yu-Han Hu, Yueh-Chiang Kim, Jihye Andreassen, Paul R. Ishiguro, Kei-ichiro Namekawa, Satoshi H. ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline |
title | ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline |
title_full | ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline |
title_fullStr | ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline |
title_full_unstemmed | ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline |
title_short | ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline |
title_sort | atf7ip2/mcaf2 directs h3k9 methylation and meiotic gene regulation in the male germline |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592865/ https://www.ncbi.nlm.nih.gov/pubmed/37873266 http://dx.doi.org/10.1101/2023.09.30.560314 |
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