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

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 JuMinho Shong, Mirang Kim, Hail Kim

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)355-368
Number of pages14
JournalDiabetes
Volume69
Issue number3
DOIs
Publication statusPublished - 2020 Mar 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kim, H., Yoon, B. H., Oh, C. M., Lee, J., Lee, K., Song, H., Kim, E., Yi, K., Kim, M. Y., Kim, H., Kim, Y. K., Seo, E. H., Heo, H., Kim, H. J., Lee, J., Suh, J. M., Koo, S. H., Seong, J. K., Kim, S., ... Kim, H. (2020). PRMT1 Is Required for the Maintenance of Mature β-Cell Identity. Diabetes, 69(3), 355-368. https://doi.org/10.2337/db19-0685