PRMT1 Is Required for the Maintenance of Mature β-Cell Identity

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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.
Publisher
AMER DIABETES ASSOC
Issue Date
2020-03
Language
English
Article Type
Article
Citation

DIABETES, v.69, no.3, pp.355 - 368

ISSN
0012-1797
DOI
10.2337/db19-0685
URI
http://hdl.handle.net/10203/272354
Appears in Collection
MSE-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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