MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice.
Three waves of H2AX phosphorylation (γH2AX) have been observed in male meiotic prophase I: the first is ATM-dependent and occurs at leptonema, while the second and third are ATR-dependent, occuring at zygonema and pachynema, respectively. The third wave of H2AX phosphorylation marks and silences uns...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007300&type=printable |
| _version_ | 1826579452076752896 |
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| author | Hanwei Jiang Qian Gao Wei Zheng Shi Yin Liu Wang Liangwen Zhong Asim Ali Teka Khan Qiaomei Hao Hui Fang Xiaoling Sun Peng Xu Tej K Pandita Xiaohua Jiang Qinghua Shi |
| author_facet | Hanwei Jiang Qian Gao Wei Zheng Shi Yin Liu Wang Liangwen Zhong Asim Ali Teka Khan Qiaomei Hao Hui Fang Xiaoling Sun Peng Xu Tej K Pandita Xiaohua Jiang Qinghua Shi |
| author_sort | Hanwei Jiang |
| collection | DOAJ |
| description | Three waves of H2AX phosphorylation (γH2AX) have been observed in male meiotic prophase I: the first is ATM-dependent and occurs at leptonema, while the second and third are ATR-dependent, occuring at zygonema and pachynema, respectively. The third wave of H2AX phosphorylation marks and silences unsynapsed chromosomes. Little is known about H2AX phosphorylation expands to chromatin-wide regions in spermatocytes. Here, we report that histone acetyltransferase (HAT) MOF is involved in all three waves of H2AX phosphorylation expansion. Germ cell-specific deletion of Mof in spermatocytes by Stra8-Cre (Mof cKO) caused global loss of H4K16ac. In leptotene and zygotene spermatocytes of cKO mice, the γH2AX signals were observed only along the chromosomal axes, and chromatin-wide H2AX phosphorylation was lost. In almost 40% of early-mid pachytene spermatocytes from Mof cKO mice, γH2AX and MDC1 were detected along the unsynapsed axes of the sex chromosomes, but failed to expand, which consequently caused meiotic sex chromosome inactivation (MSCI) failure. Furthermore, though RAD51 was proficiently recruited to double-strand break (DSB) sites, defects in DSB repair and crossover formation were observed in Mof cKO spermatocytes, indicating that MOF facilitates meiotic DSB repair after RAD51 recruitment. We propose that MOF regulates male meiosis and is involved in the expansion of all three waves of H2AX phosphorylation from the leptotene to pachytene stages, initiated by ATM and ATR, respectively. |
| first_indexed | 2024-04-12T10:01:06Z |
| format | Article |
| id | doaj.art-a9470897195649fd8307b655e74e6832 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2025-03-14T14:18:30Z |
| publishDate | 2018-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-a9470897195649fd8307b655e74e68322025-02-27T05:32:24ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-05-01145e100730010.1371/journal.pgen.1007300MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice.Hanwei JiangQian GaoWei ZhengShi YinLiu WangLiangwen ZhongAsim AliTeka KhanQiaomei HaoHui FangXiaoling SunPeng XuTej K PanditaXiaohua JiangQinghua ShiThree waves of H2AX phosphorylation (γH2AX) have been observed in male meiotic prophase I: the first is ATM-dependent and occurs at leptonema, while the second and third are ATR-dependent, occuring at zygonema and pachynema, respectively. The third wave of H2AX phosphorylation marks and silences unsynapsed chromosomes. Little is known about H2AX phosphorylation expands to chromatin-wide regions in spermatocytes. Here, we report that histone acetyltransferase (HAT) MOF is involved in all three waves of H2AX phosphorylation expansion. Germ cell-specific deletion of Mof in spermatocytes by Stra8-Cre (Mof cKO) caused global loss of H4K16ac. In leptotene and zygotene spermatocytes of cKO mice, the γH2AX signals were observed only along the chromosomal axes, and chromatin-wide H2AX phosphorylation was lost. In almost 40% of early-mid pachytene spermatocytes from Mof cKO mice, γH2AX and MDC1 were detected along the unsynapsed axes of the sex chromosomes, but failed to expand, which consequently caused meiotic sex chromosome inactivation (MSCI) failure. Furthermore, though RAD51 was proficiently recruited to double-strand break (DSB) sites, defects in DSB repair and crossover formation were observed in Mof cKO spermatocytes, indicating that MOF facilitates meiotic DSB repair after RAD51 recruitment. We propose that MOF regulates male meiosis and is involved in the expansion of all three waves of H2AX phosphorylation from the leptotene to pachytene stages, initiated by ATM and ATR, respectively.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007300&type=printable |
| spellingShingle | Hanwei Jiang Qian Gao Wei Zheng Shi Yin Liu Wang Liangwen Zhong Asim Ali Teka Khan Qiaomei Hao Hui Fang Xiaoling Sun Peng Xu Tej K Pandita Xiaohua Jiang Qinghua Shi MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. PLoS Genetics |
| title | MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. |
| title_full | MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. |
| title_fullStr | MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. |
| title_full_unstemmed | MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. |
| title_short | MOF influences meiotic expansion of H2AX phosphorylation and spermatogenesis in mice. |
| title_sort | mof influences meiotic expansion of h2ax phosphorylation and spermatogenesis in mice |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007300&type=printable |
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