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Aldosterone Alters Chromatin Structure of the Murine Endothelin‐1 Gene
Author(s) -
Welch Amanda Kuhns,
Jacobs Mollie E.,
Lynch I. Jeanette,
Gumz Michelle L.,
Cain Brian D.,
Wingo Charles S.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.911.13
Subject(s) - chromatin , biology , microbiology and biotechnology , promoter , reabsorption , gene , gene expression , endocrinology , genetics , kidney
Aldosterone (Aldo) increases sodium (Na) reabsorption in the renal collecting duct (CD) and systemic blood pressure. We have shown that Aldo induces transcription of the endothelin‐1 ( Edn1 ) gene and increases protein (ET‐1) levels (JBC 2009;294:30087). Since ET‐1 inhibits the action of Aldo on CD Na reabsorption, we hypothesize that ET‐1 acts in a negative feedback loop on Na retention. Whereas transcriptional regulation of the Edn1 gene has been investigated, the importance of epigenetic Edn1 gene regulation is largely unexplored. Here we examine the effect of Aldo on chromatin structure of the Edn1 gene. We used a novel quantitative PCR‐based DNaseI hypersensitivity assay of chromatin structure in 4 regions of the Edn1 gene known to affect transcription in murine inner medullary collecting duct‐3 cells. The calcium‐responsive element (NFAT) (JBC 2010;285:28520) at −1263 bp has low chromatin accessibility under all conditions tested. However, the NFAT element at −1563 bp upstream has low accessibility and is significantly more accessible in cells exposed to Aldo. The distal Aldo hormone response element (HRE2) is highly accessible under all conditions tested. However, Aldo caused a significant increase in chromatin accessibility of the more proximal promotor including HRE1. The results extend our previous observations and suggest that Aldo activation of the mineralocorticoid receptor (MR) results in MR binding at HRE2 to open chromatin structure of specific regions of the Edn1 gene. This work was funded by National Public Health Service Grant no. R01 DK82680 to CSW and BDC.