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Rapid genomic changes by mineralotropic hormones and kinase SIK inhibition drive coordinated renal Cyp27b1 and Cyp24a1 expression via CREB modules.


ABSTRACT: Vitamin D metabolism centers on kidney regulation of Cyp27b1 by mineralotropic hormones, including induction by parathyroid hormone (PTH), suppression by fibroblast growth factor 23 (FGF23) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and reciprocal regulations for Cyp24a1. This coordinated genomic regulation results in production of endocrine 1,25(OH)2D3, which, together with PTH and FGF23, controls mineral homeostasis. However, how these events are coordinated is unclear. Here, using in vivo chromatin immunoprecipitation sequencing in mouse kidney, we demonstrate that PTH activation rapidly induces increased recruitment of phosphorylated (p-133) CREB (pCREB) and its coactivators, CBP (CREB-binding protein) and CRTC2 (CREB-regulated tr

SUBMITTER: Meyer MB 

PROVIDER: S-EPMC9637672 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature