GLI proteins bind promoters of Hh responsive genes to promote transcription

Stable Identifier
R-HSA-5635851
Type
Pathway
Species
Homo sapiens
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GLI proteins are bifunctional DNA-binding proteins that recognize consensus GLI sites 5'-GACCACCC-3' in the promoters of target genes (Kinzler and Vogelstein, 1990). Pathway induction upon ligand-binding diverts the GLI proteins from the processing/degradation pathway that generates the truncated repressor form and promotes the formation of the full-length transcriptional activator (reviewed in Hui and Angers, 2011; Briscoe and Therond, 2013). GLI-dependent target genes have been identified by a number of ChIP based screens, and well-established, direct targets include a number of Hh pathway members including PTCH1, PTCH2, GLI1, HHIP and BOC (Lee et al, 2010; Vokes et al, 2007; Vokes et al, 2008; Agren et al, 2004; Bai et al, 2004; Bai et al, 2002; Dai et al, 1999). Full-length GLI proteins nucleate the assembly of a transcriptional activation complex at target gene promoters, but the details of interacting partners are not well known. The C-terminus of GLI3 has been shown to interact with a number of transcriptional activators including the histone acetyltransferase CBP, the Mediator component Med12 and the TATA-box recognition protein TAF31, but the detail of how and when these binding partners interact is not known (Dai et al, 1999; Zhou et al, 2006; Yoon et al, 1998; reviewed in Hui and Angers, 2011). Each of the GLI proteins has been shown to bind to CDC 73, a component of the PAF complex that has roles in RNA polymerase II-mediated transcription (Mosimann et al, 2009; reviewed in Tomson and Arndt, 2013).

Literature References
PubMed ID Title Journal Year
14723851 All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3

Bai, CB, Stephen, D, Joyner, AL

Dev. Cell 2004
21801010 Gli proteins in development and disease

Hui, CC, Angers, S

Annu. Rev. Cell Dev. Biol. 2011
10075717 Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3

Dai, P, Akimaru, H, Tanaka, Y, Maekawa, T, Nakafuku, M, Ishii, S

J. Biol. Chem. 1999
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
17000779 Mediator modulates Gli3-dependent Sonic hedgehog signaling

Zhou, H, Kim, S, Ishii, S, Boyer, TG

Mol. Cell. Biol. 2006
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
23719536 The mechanisms of Hedgehog signalling and its roles in development and disease

Briscoe, J, Thérond, PP

Nat. Rev. Mol. Cell Biol. 2013
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
12361967 Gli2, but not Gli1, is required for initial Shh signaling and ectopic activation of the Shh pathway

Bai, CB, Auerbach, W, Lee, JS, Stephen, D, Joyner, AL

Development 2002
9452474 GLI activates transcription through a herpes simplex viral protein 16-like activation domain

Yoon, JW, Liu, CZ, Yang, JT, Swart, R, Iannaccone, P, Walterhouse, D

J. Biol. Chem. 1998
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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