Ctcf is required for renin expression and maintenance of the structural integrity of the kidney.
Ctcf is required for renin expression and maintenance of the structural integrity of the kidney.
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DOI：
10.1042/cs20200184
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发表时间：
2020-07-17
期刊：
影响因子：
--
通讯作者：
Gomez RA
中科院分区：
文献类型：
--
作者：
Martinez MF;Martini AG;Sequeira-Lopez MLS;Gomez RA
肾素细胞对于血压和液体电解质稳态的调节至关重要。我们最近表明，肾素细胞在整个基因组的调节区域具有独特的染色质特征，这可能决定肾素表型的身份和记忆。染色质的 3-D 结构对于细胞身份和命运的决定可能同样重要。 CCCTC 结合因子 (Ctcf) 是一种高度保守的染色质组织者，可以通过控制染色质结构来调节肾素表型。我们发现 Ctcf 与肾素基因座周围和内部的几个保守 DNA 位点结合，表明 Ctcf 可能调节肾素细胞的转录活性。事实上，肾素谱系细胞中 Ctcf 的缺失导致肾素表达细胞的禀赋减少，并伴有循环肾素减少、低血压和肾脏严重形态异常，包括小动脉分支缺陷，并最终导致肾衰竭。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、肾素细胞数量和肾脏结构完整性的控制是必要的。
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.