GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis
Gametogenetin binding protein 2 (GGNBP2) was indispensable in normal spermatids for transformation into mature spermatozoa in mice, and when Gametogenetin binding protein 2 is bound to BRCC36 and RAD51, the complex participates in repairing DNA double-strand breaks (DSB) during the meiotic progressi...
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Taylor & Francis Group
2024-12-01
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| Series: | Epigenetics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2024.2381849 |
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| author | Kaimin Guo Yin Cao Zhiyi Zhao Jiantao Zhao Lingyun Liu Hongliang Wang |
| author_facet | Kaimin Guo Yin Cao Zhiyi Zhao Jiantao Zhao Lingyun Liu Hongliang Wang |
| author_sort | Kaimin Guo |
| collection | DOAJ |
| description | Gametogenetin binding protein 2 (GGNBP2) was indispensable in normal spermatids for transformation into mature spermatozoa in mice, and when Gametogenetin binding protein 2 is bound to BRCC36 and RAD51, the complex participates in repairing DNA double-strand breaks (DSB) during the meiotic progression of spermatocytes. Ggnbp2 knockout resulted in the up-regulation of H2AK119ubi and down-regulation of H2BK120ubi in GC-2 cells (mouse spermatogonia-derived cell line) and postnatal day 18 testis lysate. Our results also demonstrated that Gametogenetin binding protein 2 inducedASXL1 to activate the deubiquitinating enzyme BAP1 in deubiquitinating H2A, while Gametogenetin binding protein 2 knockout disrupted the interaction between ASXL1 and BAP1, resulting in BAP1 localization change. Furthermore, the Gametogenetin binding protein 2 deletion reduced H2B ubiquitination by affecting E2 enzymes and E3 ligase binding. Gametogenetin binding protein 2 regulated H2A and H2B ubiquitination levels and controlled H3K27 and H3K79 methylation by PRC2 subunits and histone H3K79 methyltransferase. Altogether, our results suggest that Ggnbp2 knockout increased DNA damage response by promoting H2A ubiquitination and H3K27trimethylation (H3K27me3) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3K79me2), revealing new mechanisms of epigenetic phenomenon during spermatogenesis. Gametogenetin binding protein 2 seems critical in regulating histone modification and chromatin structure in spermatogenesis. |
| format | Article |
| id | doaj-art-4821b0cf646f4cc4939c48b1bb522d66 |
| institution | OA Journals |
| issn | 1559-2294 1559-2308 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
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| series | Epigenetics |
| spelling | doaj-art-4821b0cf646f4cc4939c48b1bb522d662025-08-20T02:20:49ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2024.2381849GGNBP2 regulates histone ubiquitination and methylation in spermatogenesisKaimin Guo0Yin Cao1Zhiyi Zhao2Jiantao Zhao3Lingyun Liu4Hongliang Wang5Department of Andrology, First hospital of Jilin University, Changchun, ChinaDepartment of Andrology, First hospital of Jilin University, Changchun, ChinaDepartment of Andrology, First hospital of Jilin University, Changchun, ChinaDepartment of Andrology, First hospital of Jilin University, Changchun, ChinaDepartment of Andrology, First hospital of Jilin University, Changchun, ChinaDepartment of Andrology, First hospital of Jilin University, Changchun, ChinaGametogenetin binding protein 2 (GGNBP2) was indispensable in normal spermatids for transformation into mature spermatozoa in mice, and when Gametogenetin binding protein 2 is bound to BRCC36 and RAD51, the complex participates in repairing DNA double-strand breaks (DSB) during the meiotic progression of spermatocytes. Ggnbp2 knockout resulted in the up-regulation of H2AK119ubi and down-regulation of H2BK120ubi in GC-2 cells (mouse spermatogonia-derived cell line) and postnatal day 18 testis lysate. Our results also demonstrated that Gametogenetin binding protein 2 inducedASXL1 to activate the deubiquitinating enzyme BAP1 in deubiquitinating H2A, while Gametogenetin binding protein 2 knockout disrupted the interaction between ASXL1 and BAP1, resulting in BAP1 localization change. Furthermore, the Gametogenetin binding protein 2 deletion reduced H2B ubiquitination by affecting E2 enzymes and E3 ligase binding. Gametogenetin binding protein 2 regulated H2A and H2B ubiquitination levels and controlled H3K27 and H3K79 methylation by PRC2 subunits and histone H3K79 methyltransferase. Altogether, our results suggest that Ggnbp2 knockout increased DNA damage response by promoting H2A ubiquitination and H3K27trimethylation (H3K27me3) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3K79me2), revealing new mechanisms of epigenetic phenomenon during spermatogenesis. Gametogenetin binding protein 2 seems critical in regulating histone modification and chromatin structure in spermatogenesis.https://www.tandfonline.com/doi/10.1080/15592294.2024.2381849GGNBP2H2A ubiquitinationH2B ubiquitinationhistone modificationspermatogenesisDNA repair |
| spellingShingle | Kaimin Guo Yin Cao Zhiyi Zhao Jiantao Zhao Lingyun Liu Hongliang Wang GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis Epigenetics GGNBP2 H2A ubiquitination H2B ubiquitination histone modification spermatogenesis DNA repair |
| title | GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis |
| title_full | GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis |
| title_fullStr | GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis |
| title_full_unstemmed | GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis |
| title_short | GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis |
| title_sort | ggnbp2 regulates histone ubiquitination and methylation in spermatogenesis |
| topic | GGNBP2 H2A ubiquitination H2B ubiquitination histone modification spermatogenesis DNA repair |
| url | https://www.tandfonline.com/doi/10.1080/15592294.2024.2381849 |
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