scholarly journals Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 7951
Author(s):  
Sahar Waseem ◽  
Sudeep Kumar ◽  
Kanghoon Lee ◽  
Byoung-Ha Yoon ◽  
Mirang Kim ◽  
...  
Keyword(s):  
Germ Cells ◽  
Mammalian Cells ◽  
Dna Double Strand Breaks ◽  
Protein Arginine Methyltransferase ◽  
Male Germ Cells ◽  
Arginine Methyltransferase ◽  
Knock Out ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects in check point activation. Here, we generated germ cell-specific Prmt1 knock-out (KO) mice to evaluate the function of PRMT1 in spermatogenesis. Our findings demonstrate that PRMT1 is vital for male fertility in mice. Spermatogenesis in Prmt1 KO mice was arrested at the zygotene-like stage of the first meiotic division due to an elevated number of DNA double-strand breaks (DSBs). There was a loss of methylation in meiotic recombination 11 (MRE11), the key endonuclease in MRE11/RAD50/NBS 1 (MRN) complex, resulting in the accumulation of SPO11 protein in DSBs. The ATM-mediated negative feedback control over SPO11 was lost and, consequently, the repair pathway of DSBs was highly affected in PRMT1 deficient male germ cells. Our findings provide a novel insight into the role of PRMT1-mediated asymmetric demethylation in mouse spermatogenesis.

scholarly journals Dynamics of Human Protein Arginine Methyltransferase 1(PRMT1)in Vivo

2005 ◽  
Vol 280 (45) ◽  
pp. 38005-38010 ◽  
Author(s):  
Frank Herrmann ◽  
Jaeho Lee ◽  
Mark T. Bedford ◽  
Frank O. Fackelmayer
Keyword(s):  
Human Protein ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

scholarly journals Novel Functions of Protein Arginine Methyltransferase 1 in Thyroid Hormone Receptor-Mediated Transcription and in the Regulation of Metamorphic Rate in Xenopus laevis

2008 ◽  
Vol 29 (3) ◽  
pp. 745-757 ◽  
Author(s):  
Hiroki Matsuda ◽  
Bindu D. Paul ◽  
Cheol Young Choi ◽  
Takashi Hasebe ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Xenopus Laevis ◽  
Thyroid Hormone Receptor ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Frog Oocyte ◽  
Protein Arginine Methyltransferase 1 ◽  
Intestinal Remodeling ◽  
Methyltransferase 1

ABSTRACT Protein arginine methyltransferase 1 (PRMT1) acts as a transcription coactivator for nuclear receptors through histone H4 R3 methylation. The in vivo function of PRMT1 is largely unknown. Here we investigated the role of PRMT1 in thyroid hormone (T3) receptor (TR)-mediated transcription in vivo during vertebrate development. By using intestinal remodeling during T3-dependent Xenopus laevis metamorphosis for in vivo molecular analysis, we first showed that PRMT1 expression was upregulated during metamorphosis when both TR and T3 were present. We then demonstrated a role for PRMT1 in TR-mediated transcription by showing that PRMT1 enhanced transcriptional activation by liganded TR in the frog oocyte transcription system and was recruited to the T3 response element (TRE) of the target promoter in the oocyte, as well as to endogenous TREs during frog metamorphosis. Surprisingly, we found that PRMT1 was only transiently recruited to the TREs in the target during metamorphosis and observed no PRMT1 recruitment to TREs at the climax of intestinal remodeling when both PRMT1 and T3 were at peak levels. Mechanistically, we showed that overexpression of PRMT1 enhanced TR binding to TREs both in the frog oocyte model system and during metamorphosis. More importantly, transgenic overexpression of PRMT1 enhanced gene activation in vivo and accelerated both natural and T3-induced metamorphosis. These results thus indicate that PRMT1 functions transiently as a coactivator in TR-mediated transcription by enhancing TR-TRE binding and further suggest that PRMT1 has tissue-specific roles in regulating the rate of metamorphosis.

scholarly journals A Chloroacetamidine-Based Inactivator of Protein Arginine Methyltransferase 1: Design, Synthesis, and In Vitro and In Vivo Evaluation

ChemBioChem ◽  
2010 ◽  
Vol 11 (9) ◽  
pp. 1219-1223 ◽  
Author(s):  
Obiamaka Obianyo ◽  
Corey P. Causey ◽  
Tanesha C. Osborne ◽  
Justin E. Jones ◽  
Young-Ho Lee ◽  
...  
Keyword(s):  
Protein Arginine Methyltransferase ◽  
In Vivo Evaluation ◽  
Arginine Methyltransferase ◽  
Design Synthesis ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

scholarly journals Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1

2014 ◽  
Vol 24 (3) ◽  
pp. 773-786 ◽  
Author(s):  
Michael Tibshirani ◽  
Miranda L. Tradewell ◽  
Katie R. Mattina ◽  
Sandra Minotti ◽  
Wencheng Yang ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
Histone Marks ◽  
Protein Arginine Methyltransferase 1 ◽  
Methyltransferase 1

Abstract 457: Protein Arginine Methyltransferase-1 is Required for Epicardial Epithelial-to-Mesenchymal Transition

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Olan Jackson-Weaver ◽  
Jian Wu ◽  
Yongchao Gou ◽  
Shihong Shi ◽  
Henry Sucov ◽  
...  
Keyword(s):  
Cell Types ◽  
Protein Arginine Methyltransferase ◽  
Arginine Methyltransferase ◽  
P53 Expression ◽  
Epicardial Cells ◽  
Epicardial Cell ◽  
Protein Arginine Methyltransferase 1 ◽  
E Cadherin ◽  
Methyltransferase 1

Rationale: Epicardial epithelial-to-mesenchymal trasition (EMT) is a vital process in embryonic heart development. During EMT, epicardial cells acquire migratory and invasive properties, and differentiate into new cell types, including cardiac fibroblasts and coronary smooth muscle cells. EMT is characterized by an increase in mesenchymal proteins such as Slug and Fibronectin, and a decrease in cell-junction proteins such as E-Cadherin, and is dependent on TGF-β signaling. We have recently demonstrated that protein arginine methyltransferase-1 (PRMT1) is necessary for TGF-β family signaling and EMT in non-epicardial cell types. Objective: To determine the role of PRMT1 in epicardial EMT. Methods and Results: We investigated the role of PRMT1 in epicardial EMT in mouse epicardial cells. PRMT1 siRNA prevented the increase in Slug and Fibronectin and the decrease in E-Cadherin in TGF-β treatment-induced EMT of mouse epicardial cell line MEC1. PRMT1 siRNA also reduced the migration and invasion of MEC1 cells. These results demonstrate that PRMT1 is required for epicardial EMT. In WT1-Cre ERT ;ROSA-YFP fl/fl mouse embryos, PRMT1 siRNA reduced epicardial EMT in a thorax culture model. Among the key transcription factors that regulate the EMT program, Slug, but not Snail, is specifically regulated by PRMT1. We further identified that PRMT1 siRNA also increased the expression of p53, a key regulator of the Slug degradation pathway. PRMT1 siRNA increases p53 expression by decreasing p53 degradation, and shifted p53 localization to the cytoplasm. In vitro methylation assays further demonstrated that PRMT1 methylates p53. Knockdown of p53 increased Slug levels and enhanced EMT, establishing p53 as a regulator of epicardial EMT through controlling Slug expression. Conclusions: The PRMT1-p53-Slug pathway is necessary for epicardial EMT in cultured MEC1 cells as well as in the epicardium ex vivo .

Sign in / Sign up

Export Citation Format

Share Document