RETRACTED: The Chromatin-Remodeling Complex WINAC Targets a Nuclear Receptor to Promoters and Is Impaired in Williams Syndrome

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.

[1]  B. Emerson.  Specificity of Gene Regulation , 2002, Cell.

[2]  T. Kohwi-Shigematsu,et al.  SATB1 targets chromatin remodelling to regulate genes over long distances , 2002, Nature.

[3]  H. DeLuca,et al.  Cloning of the human 1 alpha,25-dihydroxyvitamin D-3 24-hydroxylase gene promoter and identification of two vitamin D-responsive elements. , 1995, Biochimica et biophysica acta.

[4]  Marleen Verhoye,et al.  Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice , 2002, Nature Genetics.

[5]  S. Lomvardas,et al.  Modifying Gene Expression Programs by Altering Core Promoter Chromatin Architecture , 2002, Cell.

[6]  M. Cole,et al.  Nuclear receptor function requires a TFTC-type histone acetyl transferase complex. , 2002, Molecular cell.

[7]  R. Poot,et al.  HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone‐fold proteins , 2000, The EMBO journal.

[8]  Tatsuya Yoshizawa,et al.  Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning , 1997, Nature Genetics.

[9]  M. Wilm,et al.  Erratum: Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II , 1997, Nature.

[10]  I. Talianidis,et al.  Coordination of PIC Assembly and Chromatin Remodeling During Differentiation-Induced Gene Activation , 2002, Science.

[11]  U. Francke,et al.  Identification of the WBSCR9 gene, encoding a novel transcriptional regulator, in the Williams-Beuren syndrome deletion at 7q11.23 , 1998, Cytogenetic and Genome Research.

[12]  R. Kingston,et al.  Cooperation between Complexes that Regulate Chromatin Structure and Transcription , 2002, Cell.

[13]  J. T. Kadonaga,et al.  Binding of Acf1 to DNA Involves a WAC Motif and Is Important for ACF-Mediated Chromatin Assembly , 2002, Molecular and Cellular Biology.

[14]  M. Fujita,et al.  hCDC47, a Human Member of the MCM Family , 1996, The Journal of Biological Chemistry.

[15]  H. Erdjument-Bromage,et al.  A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. , 1998, Genes & development.

[16]  K. Matsumoto,et al.  Induction of DNA replication by transcription in the region upstream of the human c-myc gene in a model replication system , 1996, Molecular and cellular biology.

[17]  Matthias Mann,et al.  Chromatin-remodelling factor CHRAC contains the ATPases ISWI and topoisomerase II , 1997, Nature.

[18]  Keesook Lee,et al.  Srg3, a Mouse Homolog of Yeast SWI3, Is Essential for Early Embryogenesis and Involved in Brain Development , 2001, Molecular and Cellular Biology.

[19]  Nobuyuki Itoh,et al.  Fgf10 is essential for limb and lung formation , 1999, Nature Genetics.

[20]  Myles Brown,et al.  Cofactor Dynamics and Sufficiency in Estrogen Receptor–Regulated Transcription , 2000, Cell.

[21]  G. Maul,et al.  SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. , 2002, Genes & development.

[22]  M. Muramatsu,et al.  p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone. , 2000, Genes & development.

[23]  D. Reinberg,et al.  Reconstitution of recombinant chromatin establishes a requirement for histone-tail modifications during chromatin assembly and transcription. , 2001, Genes & development.

[24]  B. Stillman,et al.  Purification and characterization of CAF-I, a human cell factor required for chromatin assembly during DNA replication in vitro , 1989, Cell.

[25]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[26]  R. Kingston,et al.  BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation , 2000, Molecular and Cellular Biology.

[27]  H. Hurst,et al.  Targeting of SWI/SNF chromatin remodelling complexes to estrogen‐responsive genes , 2002, The EMBO journal.

[28]  H. Chiba,et al.  Two human homologues of Saccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor. , 1994, Nucleic acids research.

[29]  S. Kato,et al.  Ligand-Selective Potentiation of Rat Mineralocorticoid Receptor Activation Function 1 by a CBP-Containing Histone Acetyltransferase Complex , 2002, Molecular and Cellular Biology.

[30]  Ryuji Kobayashi,et al.  ACF, an ISWI-Containing and ATP-Utilizing Chromatin Assembly and Remodeling Factor , 1997, Cell.

[31]  B. O’Malley,et al.  Sequence and Characterization of a Coactivator for the Steroid Hormone Receptor Superfamily , 1995, Science.

[32]  G. Lenoir,et al.  Elevated plasma 1,25-dihydroxyvitamin D concentrations in infants with hypercalcemia and an elfin facies. , 1985, The New England journal of medicine.

[33]  S. Kato,et al.  The Promoter of the Human 25-Hydroxyvitamin D31α-Hydroxylase Gene Confers Positive and Negative Responsiveness to PTH, Calcitonin, and 1α,25(OH)2D3☆☆☆ , 1998 .

[34]  P. Wade,et al.  WSTF–ISWI chromatin remodeling complex targets heterochromatic replication foci , 2002, The EMBO journal.

[35]  C. Glass,et al.  The coregulator exchange in transcriptional functions of nuclear receptors. , 2000, Genes & development.

[36]  G. Orphanides,et al.  Requirement of RSF and FACT for transcription of chromatin templates in vitro. , 1998, Science.

[37]  J. Nezu,et al.  A novel family of bromodomain genes. , 2000, Genomics.

[38]  S. Kato,et al.  The promoter of the human 25-hydroxyvitamin D3 1 alpha-hydroxylase gene confers positive and negative responsiveness to PTH, calcitonin, and 1 alpha,25(OH)2D3. , 1998, Biochemical and biophysical research communications.

[39]  F Randazzo,et al.  A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes. , 2000, Molecular cell.

[40]  N. Bell,et al.  Abnormal regulation of circulating 25-hydroxyvitamin D in the Williams syndrome. , 1982, The New England journal of medicine.

[41]  J. Qin,et al.  A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. , 1999, Molecular cell.

[42]  Y. Shang,et al.  Formation of the androgen receptor transcription complex. , 2002, Molecular cell.

[43]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[44]  C. Morris,et al.  A novel human gene, WSTF, is deleted in Williams syndrome. , 1998, Genomics.

[45]  J. Workman,et al.  Function and Selectivity of Bromodomains in Anchoring Chromatin-Modifying Complexes to Promoter Nucleosomes , 2002, Cell.

[46]  Thorsten Heinzel,et al.  A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors , 1996, Cell.

[47]  R. Tjian,et al.  Selectivity of chromatin-remodelling cofactors for ligand-activated transcription , 2001, Nature.