title: PRMT7 Preserves Satellite Cell Regenerative Capacity.
abstract: Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7(-/-) adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.
authors: Terry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Departments of Oncology and Medicine, McGill University, Montréal, QC H3T 1E2, Canada.
authors: Roméo Sébastien
authors: RS
authors: Blanc
authors: Terry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Departments of Oncology and Medicine, McGill University, Montréal, QC H3T 1E2, Canada.
authors: Gillian
authors: G
authors: Vogel
authors: Department of Molecular Carcinogenesis and Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
authors: Taiping
authors: T
authors: Chen
authors: Terry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Department of Human Genetics, McGill University, Montréal, QC H3T 1E2, Canada. Electronic address: colin.crist@mcgill.ca.
authors: Colin
authors: C
authors: Crist
authors: Terry Fox Molecular Oncology Group and Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montréal, QC H3T 1E2, Canada; Departments of Oncology and Medicine, McGill University, Montréal, QC H3T 1E2, Canada. Electronic address: stephane.richard@mcgill.ca.
authors: Stéphane
authors: S
authors: Richard
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002454:Cell Differentiation; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000172:deficiency / Q000235:genetics*; D012038:Regeneration / Q000235:genetics*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000097584:DNA Methyltransferase 3B
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D004248:DNA (Cytosine-5-)-Methyltransferases; D019426:Integrases; D051763:PAX7 Transcription Factor; D011484:Protein-Arginine N-Methyltransferases; D000097584:DNA Methyltransferase 3B; C493957:Cdkn1a protein, mouse; C497322:Pax7 protein, mouse; C570798:PRMT7 protein, mouse; C045073:Cre recombinase
keywords: DNMT3b; PRMT7; aging; muscle regeneration; muscle stem cell; p21CIP1; senescence