Identification of a phylogenetically conserved activin-responsive enhancer in the Zic3 gene

Multiple signaling pathways are involved in the induction of the organizer, a major center controlling vertebrate body plan formation. To study these signals, we have focused on the regulation of the Zic3 gene, which codes for a zinc finger transcription factor expressed in the organizer region at t...

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Bibliographic Details
Published in:Mechanisms of development 2003-08, Vol.120 (8), p.955-964
Main Authors: Weber, Joseph R., Sokol, Sergei Y.
Format: Article
Language:English
Subjects:
Activin
Activins - genetics
Activins - metabolism
Base Sequence
Conserved Sequence
Enhancer
Gene Expression Regulation
Gene Expression Regulation, Developmental
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Molecular Sequence Data
Nodal
Phylogeny
Promoter
Promoter Regions, Genetic
Signal Transduction
Smad2
Spemann organizer
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
Wnt
Xenopus
Zic3
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Summary:Multiple signaling pathways are involved in the induction of the organizer, a major center controlling vertebrate body plan formation. To study these signals, we have focused on the regulation of the Zic3 gene, which codes for a zinc finger transcription factor expressed in the organizer region at the beginning of gastrulation. We searched for DNA regulatory elements in the Zic3 promoter by testing their ability to drive reporter gene expression in early embryos. By this approach, we identified an activin responsive enhancer ( Zic3-ARE), which was located in the Zic3 first intron and was essential for dorsal activation of the reporter. The Zic3-ARE was stimulated by activin and Nodal ligands, but not by a dominant negative bone morphogenetic protein (BMP) receptor. The Zic3-ARE contains a repeating consensus homeodomain binding sequence, CTAATTAAA, suggesting involvement of a homeodomain transcription factor(s). Mutations in this motif abolished enhancer activity in dorsal marginal zone and its response to activin in animal pole explants. Inhibition of either Wnt/β-catenin or activin/Nodal signaling suppressed Zic3-ARE activity in dorsal blastomeres, further illustrating the importance of these pathways in activation of organizer genes.
ISSN:0925-4773
1872-6356
DOI:10.1016/S0925-4773(03)00082-0