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: Hirochika Kitagawa, Ryoji Fujiki, Kimihiro Yoshimura, Yoshihiro Mezaki, Yoshikatsu Uematsu, Daisuke Matsui, Satoko Ogawa, Kiyoe Unno, Mataichi Okubo, Akifumi Tokita, Takeya Nakagawa, Takashi Ito, Yukio Ishimi, Hiromichi Nagasawa, Toshio Matsumoto, Junn Yanagisawa, Shigeaki Kato
• Journal: Cell (Cell) Vol. 113 Issue 7 Pg. 905-17 (Jun 27 2003) ISSN: 0092-8674 [Print] United States
• PMID: 12837248 (Publication Type: Journal Article, Retracted Publication)

Chemical References

• Chromatin
• Macromolecular Substances
• Multiprotein Complexes
• Nuclear Proteins
• Nucleosomes
• Receptors, Calcitriol
• Transcription Factors

Topics

• Active Transport, Cell Nucleus (genetics)
• Animals
• Binding Sites (genetics)
• Cell Nucleus (genetics, metabolism)
• Chromatin (genetics, metabolism)
• DNA Replication (genetics)
• Eukaryotic Cells (metabolism)
• Fetus
• Gene Expression Regulation (genetics)
• Genes, Regulator (genetics)
• Humans
• Macromolecular Substances
• Mice
• Multiprotein Complexes
• Nuclear Proteins (genetics, metabolism)
• Nucleosomes (genetics)
• Promoter Regions, Genetic (genetics)
• Protein Structure, Tertiary (genetics)
• Receptors, Calcitriol (genetics, metabolism)
• S Phase (genetics)
• Transcription Factors (genetics, metabolism)
• Transcriptional Activation (genetics)
• Williams Syndrome (genetics, metabolism)