Department of Pediatrics, Child Health Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, U.S.A.
Department of Biology, University of Virginia, Charlottesville, VA 22908, U.S.A.
Clin Sci (Lond). 2020 Jul 17;134(13):1763-1774. doi: 10.1042/CS20200184.
Renin cells are crucial for the regulation of blood pressure and fluid electrolyte homeostasis. We have recently shown that renin cells possess unique chromatin features at regulatory regions throughout the genome that may determine the identity and memory of the renin phenotype. The 3-D structure of chromatin may be equally important in the determination of cell identity and fate. CCCTC-binding factor (Ctcf) is a highly conserved chromatin organizer that may regulate the renin phenotype by controlling chromatin structure. We found that Ctcf binds at several conserved DNA sites surrounding and within the renin locus, suggesting that Ctcf may regulate the transcriptional activity of renin cells. In fact, deletion of Ctcf in cells of the renin lineage led to decreased endowment of renin-expressing cells accompanied by decreased circulating renin, hypotension, and severe morphological abnormalities of the kidney, including defects in arteriolar branching, and ultimately renal failure. We conclude that control of chromatin architecture by Ctcf is necessary for the appropriate expression of renin, control of renin cell number and structural integrity of the kidney.
肾素细胞对于血压和体液电解质稳态的调节至关重要。我们最近发现，肾素细胞在整个基因组的调控区域具有独特的染色质特征，这些特征可能决定了肾素表型的身份和记忆。染色质的 3D 结构在确定细胞身份和命运方面同样重要。CCCTC 结合因子（Ctcf）是一种高度保守的染色质组织者，它可以通过控制染色质结构来调节肾素表型。我们发现 Ctcf 结合在肾素基因座周围和内部的几个保守 DNA 位点上，这表明 Ctcf 可能调节肾素细胞的转录活性。事实上，在肾素谱系细胞中删除 Ctcf 会导致表达肾素的细胞数量减少，同时伴随循环肾素减少、低血压和肾脏严重形态异常，包括小动脉分支缺陷，最终导致肾衰竭。我们的结论是，Ctcf 对染色质结构的控制对于肾素的适当表达、肾素细胞数量的控制以及肾脏的结构完整性是必要的。
