PRMT1 Is Required for the Maintenance of Mature beta-Cell Identity
- Authors
- Kim, Hyunki; Yoon, Byoung-Ha; Oh, Chang-Myung; Lee, Joonyub; Lee, Kanghoon; Song, Heein; Kim, Eunha; Yi, Kijong; Kim, Mi-Young; Kim, Hyeongseok; Kim, Yong Kyung; Seo, Eun-Hye; Heo, Haejeong; Kim, Hee-Jin; Lee, Junguee; Suh, Jae Myoung; Koo, Seung-Hoi; Seong, Je Kyung; Kim, Seyun; Ju, Young Seok; Shong, Minho; Kim, Mirang; Kim, Hail
- Issue Date
- 3월-2020
- Publisher
- AMER DIABETES ASSOC
- Citation
- DIABETES, v.69, no.3, pp.355 - 368
- Indexed
- SCIE
SCOPUS
- Journal Title
- DIABETES
- Volume
- 69
- Number
- 3
- Start Page
- 355
- End Page
- 368
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/57491
- DOI
- 10.2337/db19-0685
- ISSN
- 0012-1797
- Abstract
- 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.
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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