Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3
- Ping Dai1,2,6,
- Toshie Shinagawa1,2,6,
- Teruaki Nomura1,2,
- Jun Harada1,2,
- Sunil C. Kaul3,
- Renu Wadhwa3,
- Md Matiullah Khan1,
- Hiroshi Akimaru1,2,
- Hiroshi Sasaki4,
- Clemencia Colmenares5, and
- Shunsuke Ishii1,2,7
- 1Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 2CREST (Core Research for Science and Technology) Research Project of JST (Japan Science and Technology Corporation), Ibaraki, Japan; 3National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan; 4Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology, Kobe, Japan; 5Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
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.
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Footnotes
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↵6 These authors contributed equally to this work.
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↵7 Corresponding author.
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Supplemental material is available athttp://www.genesdev.org.
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E-MAIL sishii{at}rtc.riken.go.jp; FAX 81-298-36-9031.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1017302.
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- Received June 21, 2002.
- Accepted September 23, 2002.
- Cold Spring Harbor Laboratory Press
