title: Williams-Beuren syndrome-associated transcription factor TFII-I regulates osteogenic marker genes.
abstract: Williams-Beuren syndrome (WBS), an autosomal dominant genetic disorder, is characterized by a unique cognitive profile and craniofacial defects. WBS results from a microdeletion at the chromosomal location 7q11.23 that encompasses the genes encoding the members of TFII-I family of transcription factors. Given that the haploinsufficiency for TFII-I is causative to the craniofacial phenotype in humans, we set out to analyze the effect of post-transcriptional silencing of TFII-I during BMP-2-driven osteoblast differentiation in the C2C12 cell line. Our results show that TFII-I plays an inhibitory role in regulating genes that are essential in osteogenesis and intersects with the bone-specific transcription factor Runx2 and the retinoblastoma protein, pRb. Identification of pathways regulated by TFII-I family transcription factors may begin to shed light on the molecular determinants of WBS.
authors.affiliation: Programs in Genetics, Tufts University School of Medicine, Boston, Massachusetts 02111.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Lazebnik
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Tussie-Luna
authors.affiliation: Programs in Genetics, Tufts University School of Medicine, Boston, Massachusetts 02111; Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111. Electronic address: phinds@tuftsmedicalcenter.org.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Hinds
authors.affiliation: Programs in Genetics, Tufts University School of Medicine, Boston, Massachusetts 02111; Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111; Programs in Immunology, Tufts University School of Medicine, Boston, Massachusetts 02111. Electronic address: ananda.roy@tufts.edu.
authors.forename: Ananda L
authors.initials: AL
authors.lastname: Roy
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D019556:COS Cells; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002522:Chlorocebus aethiops; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D019473:Transcription Factors, TFII / Q000235:genetics / Q000378:metabolism*; D018980:Williams Syndrome / Q000235:genetics / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C104259:GTF2I protein, human; C486330:Gtf2i protein, mouse; C493709:RUNX2 protein, human; D016160:Retinoblastoma Protein; C493716:Runx2 protein, mouse; D019473:Transcription Factors, TFII