TY - JOUR AU - Martinez, Maria Florencia AU - Medrano, Silvia AU - Brown, Robin Isadora AU - Tufan, Turan AU - Shang, Stephen AU - Bertoncello, Nadia AU - Guessoum, Omar AU - Adli, Mazhar AU - Belyea, Brian C. AU - Sequeira-Lopez, Maria Luisa S. AU - Gomez, R. Ariel T1 - Super-enhancers maintain renin-expressing cell identity and memory to preserve multi-system homeostasis PY - 2024/02/02/ AB - Renin cells are crucial for survival — they control fluid-electrolyte and blood pressure homeostasis, vascular development, regeneration, and oxygen delivery to tissues. During embryonic development, renin cells are progenitors for multiple cell types that retain the memory of the renin phenotype. When there is a threat to survival, those descendants are transformed and reenact the renin phenotype to restore homeostasis. We tested the hypothesis that the molecular memory of the renin phenotype resides in unique regions and states of these cells’ chromatin. Using renin cells at various stages of stimulation, we identified regions in the genome where the chromatin is open for transcription, mapped histone modifications characteristic of active enhancers such as H3K27ac, and tracked deposition of transcriptional activators such as Med1, whose deletion results in ablation of renin expression and low blood pressure. Using the rank ordering of super-enhancers, epigenetic rewriting, and enhancer deletion analysis, we found that renin cells harbor a unique set of super-enhancers that determine their identity. The most prominent renin super-enhancer may act as a chromatin sensor of signals that convey the physiologic status of the organism, and is responsible for the transformation of renin cell descendants to the renin phenotype, a fundamental process to ensure homeostasis. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI121361 VL - 128 IS - 11 UR - https://doi.org/10.1172/JCI121361 SP - 4787 EP - 4803 PB - The American Society for Clinical Investigation ER -