Abstract
The heterodimeric c-Jun/c-Fos, an activator protein-1 (AP-1) has been implicated in mesoderm induction (Dong et al., 1996; Kim et al., 1998) whereas the homodimer of c-Jun was reported to be involved in neural inhibition during the early development of Xenopus embryos. During the early vertebrate development AP-1 involvement in the neural induction is still not clearly understood. We report here that AP-1 has a role in Zic3 expression, a critical proneural gene and a primary regulator of neural and neural crest development (Nakata et al., 1997; Nakata et al., 1998). AP-1 was able to induce the Zic3 gene in a dose dependent manner but other homo- or hetero-dimeric proteins, such as c-Jun/c-Jun, JunD/FosB or JunD/Fra-1 were not. The inhibition of AP-1 activity using morpholino antisenses of c-jun mRNAs blocked the Zic3 expression induced by activin. In addition, co-injection of c-jun mRNA rescued the down-regulated Zic3 expression. The promoter region of isolated Zic3 genomic DNA was found to possess several consensus-binding site of AP-1. Thus, in the functional assays, AP-1 could increase promoter activity of Zic3 gene. These findings suggest that proneural gene, Zic3 may be regulated by heterodimeric AP-1(c-Jun/c-Fos) and it may have a role in activin signaling for the regulation of neural specific gene, Zic3.
Highlights
In the functional assays, activator protein 1 (AP-1) could increase prom oter activity of Zic[3] gene. These findings suggest that proneural gene, Zic[3] m ay be regulated by heterodim eric AP-1(c-Jun/c-Fos) and it m ay have a role in activin signaling for the regulation of neural specific gene, Zic[3]
The activator protein 1 (AP-1) transcriptional complex is composed of DNA binding proteins belonging to the protooncogenes, Jun and Fos and is the dimer formed between the Jun/Jun or Jun/Fos Family of 'bzip' transcription factors
One of these, Zic[3] gene induces neural crest and proneural markers when overexpressed in animal cap explants
Summary
The activator protein 1 (AP-1) transcriptional complex is composed of DNA binding proteins belonging to the protooncogenes, Jun and Fos and is the dimer formed between the Jun/Jun or Jun/Fos Family of 'bzip' transcription factors. The Zic genes were isolated in human (Herman et al, 2002), chick, (Warner et al, 2003) Xenopus (Nakata et al, 1997; Nakata et al, 1998), Zebrafish (Grinblat et al, 2001), and Drosophilia as odd-paired (opa) gene (Cimbora et al, 1995; Aruga et al, 1996) These zinc finger proteins share a highly conserved domain consisting of five tandemly repeated C2H2-type zinc finger motifs, which have a role of DNA binding. Further investigations of loss-of-function using morpholino antisenses for c-jun mRNA and of the isolated promoter region Zic[3] genomic DNA, suggest that proneural gene, Zic[3] may be regulated by heterodimeric AP-1(c-Jun/c-Fos) and AP-1 may have a role in activin signaling for the regulation of neural specification
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