Characterization of a role of protein arginine n-methyltransferase 1 in the maintenance of pancreatic $\beta$-cell function and identity = 단백질 아르기닌 메틸화효소 1의 췌장 베타세포 기능 및 특성 유지 역할 규명에 대한 연구

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Loss of functional $\beta$-cell mass is an essential feature of type 2 diabetes, and recent studies indicate that $\beta$-cell dedifferentiation can result in the loss of functional $\beta$-cell mass. However, the mechanism underlying this $\beta$-cell dedifferentiation has not yet been elucidated. Here, we demonstrate a novel function of PRMT1 in maintaining mature $\beta$-cell function and identity. Prmt1 knock-out 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 di-methylation (H4R3me2a) and the subsequent dedifferentiation of $\beta$-cells. The expression of genes involved in mature $\beta$-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult $\beta$-cells, revealing the early feature of $\beta$-cell dedifferentiation. ChIP-seq and ATAC-seq analyses revealed that PRMT1-dependent H4R3me2a increases chromatin accessibility at the binding sites for CTCF and $\beta$-cell transcription factors. In addition, PRMT1-dependent open chromatin regions show a strong association with the risk of diabetes in humans. In conclusion, our results indicate that PRMT1 plays an essential role in maintaining $\beta$-cell identity by regulating chromatin accessibility.
Advisors
Kim, Hailresearcher김하일researcher
Description
한국과학기술원 :의과학대학원,
Publisher
한국과학기술원
Issue Date
2019
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 의과학대학원, 2019.2,[vi, 83 p. :]

Keywords

Protein arginine N-methyltransferase 1▼apancreatic $\beta$-cell▼adedifferentiation▼ahistone methylation▼achromatin; 단백질 아르기닌 메틸화 효소 1▼a췌장 베타세포▼a역분화▼a히스톤 메틸화▼a염색질

URI
http://hdl.handle.net/10203/265092
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=842192&flag=dissertation
Appears in Collection
MSE-Theses_Ph.D.(박사논문)
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