The arginine methyltransferase Prmt1 coordinates the germline arginine methylome essential for spermatogonial homeostasis and male fertility.
The arginine methyltransferase Prmt1 coordinates the germline arginine methylome essential for spermatogonial homeostasis and male fertility.
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DOI：
10.1093/nar/gkad769
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发表时间：
2023-10-27
影响因子：
14.9
通讯作者：
中科院分区：
文献类型：
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精氨酸甲基化是由精氨酸甲基转移酶（PRMTs）催化的一种常见的翻译后蛋白质修饰（PTM），参与了大量的生物学事件。然而，很少有人知道甲基精氨酸指导的信号转导在生殖细胞发育中的功能。在本研究中，我们发现Prmt 1主要分布在精原细胞的细胞核中，但在精母细胞中有微弱的分布。通过利用三种Cre介导的Prmt 1基因敲除小鼠品系的组合，我们揭示了Prmt 1对精原细胞的建立和维持是必不可少的，并且Prmt 1催化的不对称甲基精氨酸协调精原细胞内固有的转录稳态。结合高通量CUT&Tag分析和修改的小批量Smart-seq 2分析，我们揭示了Prmt 1沉积的H4 R3 me 2a标记在启动子和外显子/内含子区域被允许富集，并在小鼠精原细胞中塑造了独特的转录组景观以及选择性剪接模式。总的来说，我们的研究提供了遗传和机制的证据，连接Prmt 1沉积的甲基精氨酸信号的建立和维持高保真转录组的身份，在哺乳动物生殖细胞的精原细胞发育。
Arginine methylation, catalyzed by the protein arginine methyltransferases (PRMTs), is a common post-translational protein modification (PTM) that is engaged in a plethora of biological events. However, little is known about how the methylarginine-directed signaling functions in germline development. In this study, we discover that Prmt1 is predominantly distributed in the nuclei of spermatogonia but weakly in the spermatocytes throughout mouse spermatogenesis. By exploiting a combination of three Cre-mediated Prmt1 knockout mouse lines, we unravel that Prmt1 is essential for spermatogonial establishment and maintenance, and that Prmt1-catalyzed asymmetric methylarginine coordinates inherent transcriptional homeostasis within spermatogonial cells. In conjunction with high-throughput CUT&Tag profiling and modified mini-bulk Smart-seq2 analyses, we unveil that the Prmt1-deposited H4R3me2a mark is permissively enriched at promoter and exon/intron regions, and sculpts a distinctive transcriptomic landscape as well as the alternative splicing pattern, in the mouse spermatogonia. Collectively, our study provides the genetic and mechanistic evidence that connects the Prmt1-deposited methylarginine signaling to the establishment and maintenance of a high-fidelity transcriptomic identity in orchestrating spermatogonial development in the mammalian germline.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
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通讯作者：
Bedford, Mark T.
DOI：
10.1186/s12958-021-00828-8
发表时间：
2021-09-15
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
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作者：
Jiang X;Zhu X;Cheng Y;Azhar M;Xing X;Li W;Cao Y;Shi Q;Bao J
通讯作者：
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