Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3.
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.
Dai
Ping
P
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Ibaraki, Japan.
Shinagawa
Toshie
T
Nomura
Teruaki
T
Harada
Jun
J
Kaul
Sunil C
SC
Wadhwa
Renu
R
Khan
Md Matiullah
MM
Akimaru
Hiroshi
H
Sasaki
Hiroshi
H
Colmenares
Clemencia
C
Ishii
Shunsuke
S
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
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