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Protein Arginine Methyltransferase PRMT1 Is Essential for Palatogenesis.

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机构: [1]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China [2]Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA [3]Bioinfornatics Group, Norris Medical Library, University of Southern California, Los Angeles, CA, USA [4]Segal Cancer Center, Bloomfield Center for Research on Aging, Lady Davis Institute for Medical Research and Departments of Oncology and Medicine, McGill University, Montréal, Canada
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关键词: posttranslational modifications cleft palate signal transduction epigenetics craniofacial biology/genetics craniofacial anomalies

摘要:
Cleft palate is among the most common birth defects. Currently, only 30% of cases have identified genetic causes, whereas the etiology of the majority remains to be discovered. We identified a new regulator of palate development, protein arginine methyltransferase 1 (PRMT1), and demonstrated that disruption of PRMT1 function in neural crest cells caused complete cleft palate and craniofacial malformations. PRMT1 is the most highly expressed of the protein arginine methyltransferases, enzymes responsible for methylation of arginine motifs on histone and nonhistone proteins. PRMT1 regulates signal transduction and transcriptional activity that affect multiple signal pathways crucial in craniofacial development, such as the BMP, TGFβ, and WNT pathways. We demonstrated that Wnt1-Cre;Prmt1 fl/fl mice displayed a decrease in palatal mesenchymal cell proliferation and failure of palatal shelves to reach the midline. Further analysis in signal pathways revealed that loss of Prmt1 in mutant mice decreased BMP signaling activation and reduced the deposition of H4R3me2a mark. Collectively, our study demonstrates that Prmt1 is crucial in palate development. Our study may facilitate the development of a better strategy to interrupt the formation of cleft palate through manipulation of PRMT1 activity.

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出版当年[2018]版:
大类 | 2 区 医学
小类 | 1 区 牙科与口腔外科
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 牙科与口腔外科
第一作者:
第一作者机构: [1]State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China [2]Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
通讯作者:
通讯机构: [2]Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA [*1]Center for Craniofacial Molecular Biology, University of Southern California, 2250 Alcazar Street, CSA 106, Los Angeles, CA 90033, USA
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