PUBLICATION
Ultraconserved non-coding sequence element controls a subset of spatiotemporal GLI3 expression
- Authors
- Paparidis, Z., Abbasi, A.A., Malik, S., Goode, D.K., Callaway, H., Elgar, G., Degraaff, E., Lopez-Rios, J., Zeller, R., and Grzeschik, K.H.
- ID
- ZDB-PUB-070806-22
- Date
- 2007
- Source
- Development, growth & differentiation 49(6): 543-553 (Journal)
- Registered Authors
- Elgar, Greg, Goode, Debbie
- Keywords
- enhancer, GLI3 expression, transgenic mouse embryos, ultraconserved non-coding sequence element, zebrafish
- MeSH Terms
-
- Animals
- Base Sequence
- Cell Line, Tumor
- Conserved Sequence*
- Enhancer Elements, Genetic*
- Female
- Gene Expression Regulation, Developmental/physiology*
- Humans
- Kruppel-Like Transcription Factors/biosynthesis
- Kruppel-Like Transcription Factors/genetics*
- Male
- Mice
- Mice, Inbred CBA
- Mice, Transgenic
- Molecular Sequence Data
- Nerve Tissue Proteins/biosynthesis
- Nerve Tissue Proteins/genetics*
- Rats
- Takifugu/genetics
- Zebrafish/genetics
- PubMed
- 17661744 Full text @ Dev. Growth Diff.
Citation
Paparidis, Z., Abbasi, A.A., Malik, S., Goode, D.K., Callaway, H., Elgar, G., Degraaff, E., Lopez-Rios, J., Zeller, R., and Grzeschik, K.H. (2007) Ultraconserved non-coding sequence element controls a subset of spatiotemporal GLI3 expression. Development, growth & differentiation. 49(6):543-553.
Abstract
The zinc-finger transcription factor GLI3 acts during vertebrate development in a combinatorial, context-dependent fashion as a primary transducer of sonic hedgehog (SHH) signaling. In humans, mutations affecting this key regulator of development are associated with GLI3-morphopathies, a group of congenital malformations in which forebrain and limb development are preferentially affected. We show that a non-coding element from intron two of GLI3, ultraconserved in mammals and highly conserved in the pufferfish Fugu, is a transcriptional enhancer. In transient transfection assays, it activates reporter gene transcription in human cell cultures expressing endogenous GLI3 but not in GLI3 negative cells. The identified enhancer element is predicted to contain conserved binding sites for transcription factors crucial for developmental steps in which GLI3 is involved. The regulatory potential of this element is conserved and was used to direct tissue-specific expression of a green fluorescent protein reporter gene in zebrafish embryos and of a beta-galactosidase reporter in transgenic mouse embryos. Time, location, and quantity of reporter gene expression are congruent with part of the pattern previously reported for endogenous GLI3 transcription.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping