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Retracted: Transrepression by a liganded nuclear receptor via a bHLH activator through co‐regulator switching
Author(s) -
Murayama Akiko,
Kim Misun,
Yanagisawa Junn,
Takeyama Kenichi,
Kato Shigeaki
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600157
Subject(s) - regulator , nuclear receptor , activator (genetics) , receptor , transrepression , master regulator , negative regulator , microbiology and biotechnology , repressor , biology , chemistry , cancer research , transcription factor , signal transduction , biochemistry , transactivation , gene
Vitamin D receptor (VDR) is essential for ligand‐induced gene repression of 25(OH)D 3 1α‐hydroxylase (1α(OH)ase) in mammalian kidney, while this gene expression is activated by protein kinase A (PKA) signaling downstream of the parathyroid hormone action. The mapped negative vitamin D response element (1αnVDRE) in the human 1α(OH)ase gene promoter (around 530 bp) was distinct from those of the reported DR3‐like nVDREs, composed of two E‐box‐like motifs. Unlike the reported nVDREs, no direct binding of VDR/RXR heterodimer to 1αnVDRE was detected. A bHLH‐type factor, designated VDIR, was identified as a direct sequence‐specific activator of 1αnVDRE. The transactivation function of VDIR was further potentiated by activated‐PKA signaling through phosphorylation of serine residues in the transactivation domains, with the recruitment of a p300 histone acetyltransferase co‐activator. The ligand‐dependent association of VDR/RXR heterodimer with VDIR bound to 1αnVDRE caused the dissociation of p300 co‐activators from VDIR, and the association of HDAC co‐repressor complex components resulting in ligand‐induced transrepression. Thus, the present study deciphers a novel mechanism of ligand‐induced transrepression by nuclear receptor via co‐regulator switching.