A Gli silencer is required for robust repression of gremlin in the vertebrate limb bud.
The transcriptional response to the Hedgehog (Hh) pathway is mediated by Gli proteins, which function as context-dependent transcriptional activators or repressors. However, the mechanism by which Gli proteins regulate their target genes is poorly understood. Here, we have performed the first genetic characterization of a Gli-dependent cis-regulatory module (CRM), focusing on its regulation of Grem1 in the mouse limb bud. The CRM, termed GRE1 (Gli responsive element 1), can act as both an enhancer and a silencer. The enhancer activity requires sustained Hh signaling. As a Gli-dependent silencer, GRE1 prevents ectopic transcription of Grem1 driven through additional CRMs. In doing so, GRE1 works with additional GREs to robustly regulate Grem1. We suggest that multiple Gli CRMs may be a general mechanism for mediating a robust transcriptional response to the Hh pathway.
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA.
Qiang
Q
Li
Jordan P
JP
Lewandowski
Marian B
MB
Powell
Jacqueline L
JL
Norrie
Seung Hee
SH
Cho
Steven A
SA
Vokes
D000818:Animals; D016207:Cytokines; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D018878:Limb Buds / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics*; D000071676:Zinc Finger Protein GLI1
D016207:Cytokines; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D000071676:Zinc Finger Protein GLI1; C113178:Grem1 protein, mouse; C498520:Gli1 protein, mouse; C465570:Shh protein, mouse
Enhancer; Gli; Gremlin; Limb development; Mouse; Silencer; Sonic Hedgehog