Chromatin accessibility of kidney tubular cells under stress reveals key transcription factor mediating acute and chronic kidney disease

被引:2
作者
Xing, Yuexian [1 ,2 ]
Wang, Qi [2 ]
Zhang, Jing [2 ]
Li, Wenju [2 ]
Duan, Aiping [2 ]
Yang, Jingping [2 ,3 ]
Liu, Zhihong [1 ,2 ]
机构
[1] Southeast Univ, Jinling Hosp, Natl Clin Res Ctr Kidney Dis, Sch Med, Nanjing, Peoples R China
[2] Nanjing Univ, Jinling Hosp, Natl Clin Res Ctr Kidney Dis, Med Sch, Nanjing, Peoples R China
[3] Nanjing Univ, Med Sch, Jiangsu Key Lab Mol Med, Nanjing, Peoples R China
基金
中国国家自然科学基金;
关键词
chromatin accessibility; HNF1B; kidney disease; renal tubule; transcription reprogramming under stress; OXIDATIVE STRESS; EXPRESSION; GENE; ACTIVATION; FIBROSIS; INJURY; TUMOR; ETS-1; ACID;
D O I
10.1111/febs.15818
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cellular injury caused by stimuli plays an important role in the progression of various diseases including acute and chronic kidney diseases. The dynamic transcriptional regulation responding to stimuli underlies the important mechanism of injury. In this study, we investigated the regulatory elements and their dynamic activities in kidney tubular epithelial cells. We captured the chromatin accessibility and gene expression with ATAC-seq and RNA sequencing under a variety of extracellular stimuli including H2O2, TGF-beta 1, and FG4592 which is an agonist of hypoxia-inducible factor. Our results revealed both condition-specific and condition-shared transcription regulation. Interestingly, the shared regulation program revealed that the key transcription factor HNF1B-mediated cellular reprogramming leads to a common change among the stimuli. We found the HNF1B regulatory network was significantly disrupted in various kidney diseases.
引用
收藏
页码:5446 / 5458
页数:13
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