Open AccessA Gli silencer is required for robust repression of gremlin in the vertebrate limb bud
Author(s) -
Qiang Li,
Jordan P. Lewandowski,
Marian B. Powell,
Jacqueline L. Norrie,
Seung Hee Cho,
Steven A. Vokes
Publication year - 2014
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.15
H-Index - 36
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.104299
Subject(s) - biology , enhancer , silencer , repressor , psychological repression , limb bud , microbiology and biotechnology , transcription factor , transcription (linguistics) , context (archaeology) , hedgehog , genetics , hedgehog signaling pathway , regulation of gene expression , gene , gene expression , mechanical engineering , paleontology , linguistics , philosophy , engineering , inlet
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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