| First Author | Kim H | Year | 2020 |
| Journal | Diabetes | Volume | 69 |
| Issue | 3 | Pages | 355-368 |
| PubMed ID | 31848151 | Mgi Jnum | J:285346 |
| Mgi Id | MGI:6392577 | Doi | 10.2337/db19-0685 |
| Citation | Kim H, et al. (2020) PRMT1 Is Required for the Maintenance of Mature beta-Cell Identity. Diabetes 69(3):355-368 |
| abstractText | Loss of functional beta-cell mass is an essential feature of type 2 diabetes, and maintaining mature beta-cell identity is important for preserving a functional beta-cell mass. However, it is unclear how beta-cells achieve and maintain their mature identity. Here we demonstrate a novel function of protein arginine methyltransferase 1 (PRMT1) in maintaining mature beta-cell identity. Prmt1 knockout in fetal and adult beta-cells induced diabetes, which was aggravated by high-fat diet-induced metabolic stress. Deletion of Prmt1 in adult beta-cells resulted in the immediate loss of histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) and the subsequent loss of beta-cell identity. The expression levels of genes involved in mature beta-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult beta-cells. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing analyses revealed that PRMT1-dependent H4R3me2a increases chromatin accessibility at the binding sites for CCCTC-binding factor (CTCF) and beta-cell transcription factors. In addition, PRMT1-dependent open chromatin regions may show an association with the risk of diabetes in humans. Together, our results indicate that PRMT1 plays an essential role in maintaining beta-cell identity by regulating chromatin accessibility. |
