HDAC3 controls male fertility through enzyme-independent transcriptional regulation at the meiotic exit of spermatogenesis
| العنوان: | HDAC3 controls male fertility through enzyme-independent transcriptional regulation at the meiotic exit of spermatogenesis |
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| المؤلفون: | Yuanyuan Wang, Shuya Zhang, Chaoyang Huang, Jinwen Zhang, Joseph A. Baur, Yingwen Zhang, Xuejiang Guo, Mingyan Lin, Yanfeng Wang, Huiqi Yin, Hua Feng, Ke Zheng, P. Jeremy Wang, Yichun Guan, Zhenlong Kang, Yihan Zhang, Lan Ye, Mengrou Liu, Zheng Sun, Qiushi Xu, Changpeng Xin, Wenxiu He, Bangjin Zheng, Yanfeng Xue, Jie Xie, Yingyun Gong, Kaiqiang Fu |
| المصدر: | Nucleic Acids Research |
| بيانات النشر: | Oxford University Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Transcriptional Activation, AcademicSubjects/SCI00010, Biology, Genome Integrity, Repair and Replication, Histone Deacetylases, Histones, 03 medical and health sciences, Mice, 0302 clinical medicine, Testis, Genetics, Transcriptional regulation, Animals, Spermatogenesis, SOX Transcription Factors, 030304 developmental biology, Epigenomics, Regulation of gene expression, Mice, Knockout, 0303 health sciences, Acetylation, HDAC3, Cellular Reprogramming, Spermatids, Cell biology, Mice, Inbred C57BL, Meiosis, Histone, Fertility, Cistrome, Gene Expression Regulation, biology.protein, Histone deacetylase, 030217 neurology & neurosurgery |
| الوصف: | The transition from meiotic spermatocytes to postmeiotic haploid germ cells constitutes an essential step in spermatogenesis. The epigenomic regulatory mechanisms underlying this transition remain unclear. Here, we find a prominent transcriptomic switch from the late spermatocytes to the early round spermatids during the meiotic-to-postmeiotic transition, which is associated with robust histone acetylation changes across the genome. Among histone deacetylases (HDACs) and acetyltransferases, we find that HDAC3 is selectively expressed in the late meiotic and early haploid stages. Three independent mouse lines with the testis-specific knockout of HDAC3 show infertility and defects in meiotic exit with an arrest at the late stage of meiosis or early stage of round spermatids. Stage-specific RNA-seq and histone acetylation ChIP-seq analyses reveal that HDAC3 represses meiotic/spermatogonial genes and activates postmeiotic haploid gene programs during meiotic exit, with associated histone acetylation alterations. Unexpectedly, abolishing HDAC3 catalytic activity by missense mutations in the nuclear receptor corepressor (NCOR or SMRT) does not cause infertility, despite causing histone hyperacetylation as HDAC3 knockout, demonstrating that HDAC3 enzyme activity is not required for spermatogenesis. Motif analysis of the HDAC3 cistrome in the testes identified SOX30, which has a similar spatiotemporal expression pattern as HDAC3 during spermatogenesis. Depletion of SOX30 in the testes abolishes the genomic recruitment of the HDAC3 to the binding sites. Collectively, these results establish the SOX30/HDAC3 signaling as a key regulator of the transcriptional program in a deacetylase-independent manner during the meiotic-to-postmeiotic transition in spermatogenesis. |
| اللغة: | English |
| تدمد: | 1362-4962 0305-1048 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fee828edf13c68ae1a2d1d2e3e1bbe7 http://europepmc.org/articles/PMC8136829 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3fee828edf13c68ae1a2d1d2e3e1bbe7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13624962 03051048 |
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