CTCF公司
粘蛋白
染色质
基因组
细胞生物学
生物
染色体构象捕获
遗传学
转录因子
增强子
计算生物学
基因
作者
Kushagra Bansal,Daniel A. Michelson,Ricardo N. Ramírez,Aaron D. Viny,Ross L. Levine,Christophe Benoist,Diane Mathis
标识
DOI:10.1073/pnas.2110991118
摘要
Significance Aire controls immunological tolerance by driving promiscuous expression of a large swath of the genome in medullary thymic epithelial cells (mTECs). Its molecular mechanism remains enigmatic. To address the hypothesis that Aire impacts chromatin organization through widespread promotion of superenhancer–promoter loops, we performed genome-wide, high-resolution chromosome-conformation capture (Hi-C) experiments on ex vivo mTECs from thymi of mice expressing Aire or not. Integration of the resulting data with inventories of the genome-wide locations of Aire, subunits of the mediator and cohesin complexes, and the chromatin-domain enforcer, CCCTC-binding factor (CTCF), indeed argued for a looping model, which was further supported by biochemical and in vivo loss-of-function analyses.
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