RETRACTED: 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.

Id2 gene-targeted crosstalk between Wnt and retinoid signaling regulates proliferation in human keratinocytes

“…The protein composition of these complexes determines the overall transcriptional effect exerted by the receptor (Yanagisawa et al, 2002;Kitagawa et al, 2003;Ohtake et al, 2003). Interaction of retinoid receptors with b-catenin at the Id2 gene WRE presumably leads to recruitment of repressor complexes containing histone deacetylase and demethylase activities.…”

The genomic basis of the Williams – Beuren syndrome

“…The BAZ1B protein (alias WSTF: Williams syndrome transcription factor) is a component of ATP-dependent chromatin remodelling complexes WINAC (WSTF Including Nucleosome Assembly Complex); these complexes are required in many nuclear processes such as replication, transcription and chromatin maintenance [144 -146]. Furthermore, the WINAC complex interacts with the vitamin D receptor via ligand-induced transactivation of the receptor [147]. BAZ1B is expressed differentially in neural tissue and it is subcellularly localized to condensed chromatin.…”

“…Based on results from knock out mice studies, from in vitro assays on gene expression and from clinical findings in patients with only partial deletions of the WBS region, the genes LIMK1, CLIP2 (alias CYLN2) and the two members of TFII-I transcription family (GTF2IRD1 and GTF2I) are identified as playing the major role in developing the cognitive features [12, 43, 93 -95, 179, 186, 188]. Furthermore there are some hints that haploinsufficiency of BAZ1B may contribute to the hypercalcaemia in infants with WBS [147].…”

Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing

“…A more common, reversely connected motif, the PHD finger-bromodomain, is found in many chromatinassociated proteins including histone lysine methyl-transferase MLL1 (ref. 28), Williams syndrome transcription factor (WSTF) in the chromatin-remodeling complex WINAC 29 , and the TIF1 family proteins (α, β, γ and δ; note that TIF1β is also known as KAP1 or TRIM28) 30 . This tandem PHD finger-bromodomain is also found in Sp140, a leukocytespecific protein in the nuclear body that is involved in the pathogenesis of acute promyelocytic leukemia and viral infection 31 .…”