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Publication : A Gli silencer is required for robust repression of gremlin in the vertebrate limb bud.

First Author  Li Q Year  2014
Journal  Development Volume  141
Issue  9 Pages  1906-14
PubMed ID  24700818 Mgi Jnum  J:207959
Mgi Id  MGI:5560163 Doi  10.1242/dev.104299
Citation  Li Q, et al. (2014) A Gli silencer is required for robust repression of gremlin in the vertebrate limb bud. Development 141(9):1906-14
abstractText  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.
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