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- Title
Protein Arginine Methyltransferase PRMT1 Is Essential for Palatogenesis.
- Authors
Gou, Y.; Li, J.; Jackson-Weaver, O.; Wu, J.; Zhang, T.; Gupta, R.; Cho, I.; Ho, T. V.; Chen, Y.; Li, M.; Richard, S.; Wang, J.; Chai, Y.; Xu, J.
- Abstract
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.
- Subjects
CLEFT palate; PROTEIN arginine methyltransferases; PALATE; MORPHOGENESIS; HUMAN abnormality genetics; NEURAL crest; CRANIOFACIAL abnormalities; NONHISTONE chromosomal proteins
- Publication
Journal of Dental Research, 2018, Vol 97, Issue 13, p1510
- ISSN
0022-0345
- Publication type
journal article
- DOI
10.1177/0022034518785164