title: The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome.
abstract: We identified a human multiprotein complex (WINAC) that directly interacts with the vitamin D receptor (VDR) through the Williams syndrome transcription factor (WSTF). WINAC has ATP-dependent chromatin-remodeling activity and contains both SWI/SNF components and DNA replication-related factors. The latter might explain a WINAC requirement for normal S phase progression. WINAC mediates the recruitment of unliganded VDR to VDR target sites in promoters, while subsequent binding of coregulators requires ligand binding. This recruitment order exemplifies that an interaction of a sequence-specific regulator with a chromatin-remodeling complex can organize nucleosomal arrays at specific local sites in order to make promoters accessible for coregulators. Furthermore, overexpression of WSTF could restore the impaired recruitment of VDR to vitamin D regulated promoters in fibroblasts from Williams syndrome patients. This suggests that WINAC dysfunction contributes to Williams syndrome, which could therefore be considered, at least in part, a chromatin-remodeling factor disease.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032, Tokyo, Japan.
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fujiki
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mezaki
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Uematsu
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsui
authors.forename: Satoko
authors.initials: S
authors.lastname: Ogawa
authors.forename: Kiyoe
authors.initials: K
authors.lastname: Unno
authors.forename: Mataichi
authors.initials: M
authors.lastname: Okubo
authors.forename: Akifumi
authors.initials: A
authors.lastname: Tokita
authors.forename: Takeya
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishimi
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D005333:Fetus; D005786:Gene Expression Regulation / Q000235:genetics; D005809:Genes, Regulator / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D016196:S Phase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics; D018980:Williams Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D009707:Nucleosomes; D018167:Receptors, Calcitriol; D014157:Transcription Factors