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GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis.
- Source :
-
Epigenetics [Epigenetics] 2024 Dec; Vol. 19 (1), pp. 2381849. Date of Electronic Publication: 2024 Aug 07. - Publication Year :
- 2024
-
Abstract
- 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 H2A <subscript>K119ubi</subscript> and down-regulation of H2B <subscript>K120ubi</subscript> 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 H3 <subscript>K27</subscript> and H3 <subscript>K79</subscript> methylation by PRC2 subunits and histone H3K79 methyltransferase. Altogether, our results suggest that Ggnbp2 knockout increased DNA damage response by promoting H2A ubiquitination and H3 <subscript>K27</subscript> trimethylation (H3 <subscript>K27me3</subscript> ) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3 <subscript>K79me2</subscript> ), revealing new mechanisms of epigenetic phenomenon during spermatogenesis. Gametogenetin binding protein 2 seems critical in regulating histone modification and chromatin structure in spermatogenesis.
- Subjects :
- Animals
Male
Mice
Cell Line
Methylation
Mice, Knockout
Repressor Proteins metabolism
Repressor Proteins genetics
Tumor Suppressor Proteins metabolism
Tumor Suppressor Proteins genetics
Ubiquitin Thiolesterase metabolism
Ubiquitin Thiolesterase genetics
Histones metabolism
Spermatogenesis genetics
Ubiquitination
Subjects
Details
- Language :
- English
- ISSN :
- 1559-2308
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 39109527
- Full Text :
- https://doi.org/10.1080/15592294.2024.2381849