Ligand-induced transrepressive function of VDR requires a chromatin remodeling complex, WINAC.
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) 1alpha-hydroxylase [1alpha(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 1alpha(OH)ase gene. Thus, our findings indicate that WINAC associates with chromatin through a physical interaction between the WSTF bromodomain and acetylated histones, that appears to be indispensable for VDR/promoter association for ligand-induced transrepression of 1alpha(OH)ase gene expression.
Kato
Shigeaki
S
The Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. uskato@mail.ecc.u-tokyo.ac.jp
Fujiki
Ryoji
R
Kim
Mi-Sun
MS
Kitagawa
Hirochika
H
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000107:Acetylation; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008024:Ligands; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism; D018980:Williams Syndrome / Q000378:metabolism
D006657:Histones; D008024:Ligands; D018167:Receptors, Calcitriol; D014157:Transcription Factors; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase