title: Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3.
abstract: Transcription factor Glioblastoma-3 (Gli3) is cleaved in the anterior region of the limb bud to generate its repressor form. In contrast, Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity blocks Gli3 processing and then induces the expression of Gli3 target genes, including Gli1. Here we report that the Ski corepressor binds to Gli3 and recruits the histone deacetylase complex. The Gli3-mediated repression was impaired by anti-Ski antibody and in Ski-deficient fibroblasts, and Shh-induced Gli1 gene transcription mediated by full-length Gli3 was inhibited by Ski. Furthermore, a Ski mutation enhanced the digit abnormalities caused by the Gli3 gene mutation. Thus, Ski plays an important role in pattern formation.
authors.affiliation: Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Ibaraki, Japan.
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.forename: Toshie
authors.initials: T
authors.lastname: Shinagawa
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nomura
authors.forename: Jun
authors.initials: J
authors.lastname: Harada
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Md Matiullah
authors.initials: MM
authors.lastname: Khan
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akimaru
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Clemencia
authors.initials: C
authors.lastname: Colmenares
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005347:Fibroblasts / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D017880:Limb Deformities, Congenital / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3
chemical_list: D000906:Antibodies; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D012097:Repressor Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3; C446031:rasp protein, Drosophila; D000217:Acyltransferases; D006655:Histone Deacetylases