染色质
急性肾损伤
转录因子
染色质重塑
肾
生物
细胞生物学
DNA修复
医学
癌症研究
生物信息学
基因
遗传学
内科学
作者
Xinyi Cao,Jiuchen Wang,Tianye Zhang,Zhiheng Liu,Lijun Liu,Ying Chen,Zehua Li,Yutong Zhao,Qi Yu,Tong Liu,Jing Nie,Yuanjie Niu,Yupeng Chen,Li Yang,Lirong Zhang
标识
DOI:10.1038/s41467-022-34854-w
摘要
Abstract Renal tubular epithelial cells (TECs) can initiate an adaptive response to completely recover from mild acute kidney injury (AKI), whereas severe injury often leads to persistence of maladaptive repair and progression to kidney fibrosis. Through profiling of active DNA regulatory elements by ATAC-seq, we reveal widespread, dynamic changes in the chromatin accessibility of TECs after ischemia–reperfusion injury. We show that injury-specific domains of regulatory chromatin become accessible prior to gene activation, creating poised chromatin states to activate the consequent gene expression program and injury response. We further identify RXRα as a key transcription factor in promoting adaptive repair. Activation of RXRα by bexarotene, an FDA-approved RXRα agonist, restores the chromatin state and gene expression program to protect TECs against severe kidney injury. Together, our findings elucidate a chromatin-mediated mechanism underlying differential responses of TECs to varying injuries and identify RXRα as a therapeutic target of acute kidney injury.
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