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Retracted: Ligand‐induced transrepression by VDR through association of WSTF with acetylated histones
Author(s) -
Fujiki Ryoji,
Kim Misun,
Sasaki Yasumasa,
Yoshimura Kimihiro,
Kitagawa Hirochika,
Kato Shigeaki
Publication year - 2005
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.7600853
Subject(s) - biology , acetylation , transrepression , histone , ligand (biochemistry) , genetics , computational biology , transcription factor , receptor , gene , transactivation
We have previously shown that the novel ATP‐dependent chromatin‐remodeling complex WINAC is required for the ligand‐bound vitamin D receptor (VDR)‐mediated transrepression of the 25(OH)D 3 1α‐hydroxylase (1α(OH)ase) gene. However, the molecular basis for VDR promoter association, which does not involve its binding to specific DNA sequences, remains unclear. To address this issue, we investigated the function of WSTF in terms of the association between WINAC and chromatin for ligand‐induced transrepression by VDR. Results of in vitro experiments using chromatin templates showed that the association of unliganded VDR with the promoter required physical interactions between WSTF and both VDR and acetylated histones prior to VDR association with chromatin. The acetylated histone‐interacting region of WSTF was mapped to the bromodomain, and a WSTF mutant lacking the bromodomain served as a dominant‐negative mutant in terms of ligand‐induced transrepression of the 1α(OH)ase gene. Thus, our findings indicate that WINAC associates with chromatin through a physical interaction between the WSTF bromodomain and acetylated his tones, which appears to be indispensable for VDR/promoter association for ligand‐induced transrepression of 1α(OH)ase gene expression.