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- Title
PRMT1 Is Required for the Maintenance of Mature β-Cell Identity.
- Authors
Hyunki Kim; Byoung-Ha Yoon; Chang-Myung Oh; Joonyub Lee; Kanghoon Lee; Heein Song; Eunha Kim; Kijong Yi; Mi-Young Kim; Hyeongseok Kim; Yong Kyung Kim; Eun-Hye Seo; Haejeong Heo; Hee-Jin Kim; Junguee Lee; Jae Myoung Suh; Seung-Hoi Koo; Je Kyung Seong; Seyun Kim; Young Seok Ju
- Abstract
Loss of functional β-cell mass is an essential feature of type 2 diabetes, and maintaining mature β-cell identity is important for preserving a functional β-cell mass. However, it is unclear how β-cells achieve and maintain their mature identity. Here we demonstrate a novel function of protein arginine methyltransferase 1 (PRMT1) in maintaining mature β-cell identity. Prmt1 knockout in fetal and adult β-cells induced diabetes, which was aggravated by high-fat diet-induced metabolic stress. Deletion of Prmt1 in adult β-cells resulted in the immediate loss of histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) and the subsequent loss of β-cell identity. The expression levels of genes involved in mature β-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult β-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 β-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 β-cell identity by regulating chromatin accessibility.
- Subjects
PROTEIN arginine methyltransferases; TYPE 2 diabetes; TRANSCRIPTION factors; DEPERSONALIZATION; ARGININE; BINDING sites; DNA methyltransferases; PROTEIN metabolism; GLUCOSE intolerance; CHROMOSOMES; BIOCHEMISTRY; CELL differentiation; GENETICS; ANIMAL experimentation; ISLANDS of Langerhans; PHENOMENOLOGY; GENES; TRANSFERASES; METHYLATION; GENETIC techniques; MICE
- Publication
Diabetes, 2020, Vol 69, Issue 3, p355
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db19-0685