GLI3R binds the PTCH1 promoter

Stable Identifier
R-HSA-5612508
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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GLI3R is a DNA-binding transcriptional repressor that recognizes consensus GLI sites 5'-GACCACCC-3' in the promoters of target genes (Kinzler and Vogelstein, 1990). DNA-binding is mediated through 5 C2H2 Kruppel zinc fingers in the N-terminal region of the protein, which remains intact after proteasome-mediated processing (reviewed in Hui and Angers, 2011). GLI-dependent target genes have been identified by a number of ChIP based screens, and one well established target of GLI3R is the Hh receptor, PTCH1 (Lee et al, 2010; Vokes et al, 2007; Vokes et al, 2008). GLI3R has been shown to bind to a GLI-consensus sequence in the PTCH1 promoter as assesed by electrophoretic mobility shift assay and the protein is able to repress expression of a reporter gene driven by this element (Agren et al, 2004). GLI3R may promote repressive complexes at the PTCH1 promoter by the SKI1-dependent recruitment of HDAC complexes (Dai et al, 2002). Other GLI3R transcriptional targets include GLI1 and GLI2 (Hu et al, 2006).

Literature References
PubMed ID Title Journal Year
21801010 Gli proteins in development and disease

Hui, CC, Angers, S

Annu. Rev. Cell Dev. Biol. 2011
16396903 GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis

Hu, MC, Mo, R, Bhella, S, Wilson, CW, Chuang, PT, Hui, CC, Rosenblum, ND

Development 2006
12435627 Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3

Dai, P, Shinagawa, T, Nomura, T, Harada, J, Kaul, SC, Wadhwa, R, Khan, MM, Akimaru, H, Sasaki, H, Colmenares, C, Ishii, S

Genes Dev. 2002
17442700 Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning

Vokes, SA, Ji, H, McCuine, S, Tenzen, T, Giles, S, Zhong, S, Longabaugh, WJ, Davidson, EH, Wong, WH, McMahon, AP

Development 2007
2105456 The GLI gene encodes a nuclear protein which binds specific sequences in the human genome

Kinzler, KW, Vogelstein, B

Mol. Cell. Biol. 1990
18832070 A genome-scale analysis of the cis-regulatory circuitry underlying sonic hedgehog-mediated patterning of the mammalian limb

Vokes, SA, Ji, H, Wong, WH, McMahon, AP

Genes Dev. 2008
15087129 Expression of the PTCH1 tumor suppressor gene is regulated by alternative promoters and a single functional Gli-binding site

Agren, M, Kogerman, P, Kleman, MI, Wessling, M, Toftgård, R

Gene 2004
20460306 Hedgehog pathway-regulated gene networks in cerebellum development and tumorigenesis

Lee, EY, Ji, H, Ouyang, Z, Zhou, B, Ma, W, Vokes, SA, McMahon, AP, Wong, WH, Scott, MP

Proc. Natl. Acad. Sci. U.S.A. 2010
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