Title | RPA1 controls chromatin architecture and maintains lipid metabolic homeostasis |
Authors | Yin, Qi Li, Yang Zhou, Zhe Zhou, Zhe Li, Xiang Li, Minghao Liu, Chengyang Dong, Di Wang, Guangxi Zhu, Minglu Yang, Jingyi Jin, Yan Guo, Limei Yin, Yuxin |
Affiliation | Peking Univ, Peking Tsinghua Ctr Life Sci, Sch Basic Med Sci, Inst Syst Biomed,Dept Pathol,Hlth Sci Ctr, Beijing 100191, Peoples R China Peking Univ, Shenzhen Hosp, Inst Precis Med, Shenzhen 518036, Peoples R China Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China |
Keywords | REPLICATION PROTEIN-A SINGLE-STRANDED-DNA R LOOPS BINDING LANDSCAPE DAMAGE NAFLD SEQ |
Issue Date | 12-Jul-2022 |
Publisher | CELL REPORTS |
Abstract | Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, with a prevalence of 25% worldwide. However, the underlying molecular mechanism involved in the development and progression of the NAFLD spectrum remains unclear. Single-stranded DNA-binding protein replication protein A1 (RPA1) participates in DNA replication, recombination, and damage repair. Here, we show that Rpa1(+/-) mice develop fatty liver disease during aging and in response to a high-fat diet. Liver-specific deletion of Rpa1 results in down-regulation of genes related to fatty acid oxidation and impaired fatty acid oxidation, which leads to hepatic steatosis and hepatocellular carcinoma. Mechanistically, RPA1 binds gene regulatory regions, chromatin-remodeling factors, and HNF4A and remodels chromatin architecture, through which RPA1 promotes HNF4A transcriptional activity and fatty acid beta oxidation. Collectively, our data demonstrate that RPA1 is an important regulator of NAFLD through controlling chromatin accessibility. |
URI | http://hdl.handle.net/20.500.11897/649359 |
ISSN | 2211-1247 |
DOI | 10.1016/j.celrep.2022.111071 |
Indexed | SCI(E) |
Appears in Collections: | 基础医学院 深圳医院 天然药物与仿生药物国家重点实验室 |