AUTHOR=Dong Fangfang , Chen Min , Chen Min , Jiang Lin , Shen Zhiming , Ma Longfei , Han Chunsheng , Guo Xudong , Gao Fei 

TITLE=PRMT5 Is Involved in Spermatogonial Stem Cells Maintenance by Regulating Plzf Expression via Modulation of Lysine Histone Modifications

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.673258

DOI=10.3389/fcell.2021.673258

ISSN=2296-634X

ABSTRACT=<p>Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of mono- or symmetric dimethylarginine residues on histones and non-histone substrates and has been demonstrated to play important roles in many biological processes. In the present study, we observed that PRMT5 is abundantly expressed in spermatogonial stem cells (SSCs) and that <italic>Prmt5</italic> deletion results in a progressive loss of SSCs and male infertility. The proliferation of <italic>Prmt5</italic>-deficient SSCs cultured <italic>in vitro</italic> exhibited abnormal proliferation, cell cycle arrest in G0/G1 phase and a significant increase in apoptosis. Furthermore, PLZF expression was dramatically reduced in <italic>Prmt5</italic>-deficient SSCs, and the levels of H3K9me2 and H3K27me2 were increased in the proximal promoter region of the <italic>Plzf</italic> gene in <italic>Prmt5</italic>-deficient SSCs. Further study revealed that the expression of lysine demethylases (JMJD1A, JMJD1B, JMJD1C, and KDM6B) was significantly reduced in <italic>Prmt5</italic>-deficient SSCs and that the level of permissive arginine methylation H3R2me2s was significantly decreased at the upstream promoter region of these genes in <italic>Prmt5</italic>-deficient SSCs. Our results demonstrate that PRMT5 regulates spermatogonial stem cell development by modulating histone H3 lysine modifications.</p>