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Lysine acetyltransferases cyclic adenosine monophosphate response element‐binding binding protein and acetyltransferase p300 attenuate transcriptional activity of the mineralocorticoid receptor through its acetylation
Author(s) -
Seo Minchul,
Song Minji,
Seok Young Mi,
Kang Seol Hee,
Lee Hae Ahm,
Sohn Uy Dong,
Kim In Kyeom
Publication year - 2015
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12377
Subject(s) - acetyltransferase , acetylation , chromatin immunoprecipitation , p300 cbp transcription factors , histone acetyltransferases , pcaf , microbiology and biotechnology , acetyltransferases , histone acetyltransferase , lysine , creb binding protein , biology , immunoprecipitation , mineralocorticoid receptor , chemistry , biochemistry , gene expression , transcription factor , receptor , promoter , gene , creb , amino acid
Summary Acetylation of the mineralocorticoid receptor ( MR ) by inhibition of lysine deacetylases attenuates MR 's transcriptional activity. However, the specific lysine acetyltransferases that are responsible for acetylation of the MR remain unknown. We hypothesized that the acetyltransferases cyclic adenosine monophosphate response element‐binding binding protein ( CBP ) and acetyltransferase p300 (p300) attenuate transcriptional activity of the MR through its acetylation. Expression of MR target genes was measured by quantitative real‐time polymerase chain reaction. Recruitment of MR and RNA polymerase II (Pol II) on promoters of target genes was analysed by chromatin immunoprecipitation. Acetylation of the MR was determined by western blot with an anti‐acetyl‐lysine antibody after immunoprecipitation with an anti‐ MR antibody. In human embryonic kidney (HEK) 293 cells, overexpression of CBP or p300, but not p300/ CBP ‐associated factor, increased MR acetylation and decreased expression of MR target genes. The downregulation of target genes coincided with a decrease in the recruitment of MR and Pol II to specific hormone response elements. These results demonstrate that overexpression of CBP or p300 attenuates the transcriptional activity of the MR through its acetylation in HEK 293 cells. Our data provide strong evidence identifying CBP and p300 as lysine acetyltransferases responsible for the regulation of MR that may provide new therapeutic targets for the treatment of hypertension.