[HTML][HTML] Non-consensus GLI binding sites in Hedgehog target gene regulation
M Winklmayr, C Schmid, S Laner-Plamberger… - BMC molecular …, 2010 - Springer
M Winklmayr, C Schmid, S Laner-Plamberger, A Kaser, F Aberger, T Eichberger…
BMC molecular biology, 2010•SpringerBackground The GLI transcription factors, mediators of the hedgehog signal bind with high
affinity to the consensus sequence GACCACCCA. The affinity of variant single substitutions
in GLI binding sites has been measured systematically, but the affinities of the variant
binding sites appears low compared to the frequency of occurrence of variant sites in known
GLI target gene promoters. Results We quantified transcriptional activation by GLI using
PTCH1 promoter based luciferase reporters containing all single substitutions of the GLI …
affinity to the consensus sequence GACCACCCA. The affinity of variant single substitutions
in GLI binding sites has been measured systematically, but the affinities of the variant
binding sites appears low compared to the frequency of occurrence of variant sites in known
GLI target gene promoters. Results We quantified transcriptional activation by GLI using
PTCH1 promoter based luciferase reporters containing all single substitutions of the GLI …
Background
The GLI transcription factors, mediators of the hedgehog signal bind with high affinity to the consensus sequence GACCACCCA. The affinity of variant single substitutions in GLI binding sites has been measured systematically, but the affinities of the variant binding sites appears low compared to the frequency of occurrence of variant sites in known GLI target gene promoters.
Results
We quantified transcriptional activation by GLI using PTCH1 promoter based luciferase reporters containing all single substitutions of the GLI consensus binding site. As expected variants with very low affinity did not activate the reporter. Many lower affinity binding sequences are, however, functional in the presence of moderate GLI concentration. Using two natural non-consensus GLI site promoters we showed that substitution of the variant sequences by consensus leads to comparable activity.
Conclusions
Variant GLI binding sites with relatively low affinity can within natural promoters lead to strong transcriptional activation. This may facilitate the identification of additional direct GLI target genes.
Springer