NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor

Ayano Murai-Takeda, Hirotaka Shibata, Isao Kurihara, Sakiko Kobayashi, Kenichi Yokota, Noriko Suda, Yuko Mitsuishi, Rie Jo, Hirochika Kitagawa, Shigeaki Kato, Takao Saruta, Hiroshi Itoh

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30 Citations (Scopus)


The role of aldosterone has been implicated in the metabolic syndrome and cardiovascular diseases. The biological actions of aldosterone are mediated through mineralocorticoid receptor (MR). Nuclear receptor-mediated gene expression is regulated by dynamic and coordinated recruitment of coactivators and corepressors. To identify new coregulators of the MR, full-length MR was used as bait in yeast two-hybrid screening. Weisolated NF-YC, one of the subunits of heterotrimeric transcription factor NF-Y. Specific interaction between MRand NF-YC was confirmed by yeast two-hybrid, mammalian two-hybrid, coimmunoprecipitation assays, and fluorescence subcellular imaging. Transient transfection experiments in COS-7 cells demonstrated that NF-YC repressed MR transactivation in a hormone-sensitive manner. Moreover, reduction of NF-YC protein levels by small interfering RNA potentiated hormonal activation of endogenous target genes in stably MR-expressing cells, indicating that NF-YC functions as an agonist-dependent MR corepressor. The corepressor function of NF-YC is selective for MR, because overexpression of NF-YC did not affect transcriptional activity mediated by androgen, progesterone, or glucocorticoid receptors. Chromatin immunoprecipitation experiments showed that endogenous MR and steroid receptor coactivator-1 were recruited to an endogenous ENaC gene promoter in a largely aldosterone-dependent manner, and endogenous NF-YC was sequentially recruited to the same element. Immunohistochemistry showed that endogenous MR and NF-YC were colocalized within the mouse kidney. Although aldosterone induces interaction of the N and C termini of MR, NF-YC inhibited the N/C interaction. These findings indicate that NF-YC functions as a new corepressor of agonist-bound MR via alteration of aldosterone-induced MR conformation.

Original languageEnglish
Pages (from-to)8084-8093
Number of pages10
JournalJournal of Biological Chemistry
Issue number11
Publication statusPublished - 2010 Mar 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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