1.Transcriptional regulation of Zic3 by heterodimeric AP-1(c-Jun/c-Fos) during Xenopus development.
Sung Young LEE ; Hyun Shik LEE ; Jin Soo MOON ; Jong Il KIM ; Jae Bong PARK ; Jae Yong LEE ; Mae Ja PARK ; Jaebong KIM
Experimental & Molecular Medicine 2004;36(5):468-475
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.
Activins/pharmacology/physiology
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Animals
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Base Sequence
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Binding Sites/genetics
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Consensus Sequence/genetics
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Dimerization
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Embryo, Nonmammalian/metabolism
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*Gene Expression Regulation, Developmental
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Homeodomain Proteins/*genetics
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Molecular Sequence Data
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Promoter Regions (Genetics)/genetics
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Proto-Oncogene Proteins c-fos/genetics/physiology
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Proto-Oncogene Proteins c-jun/genetics/physiology
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RNA, Antisense/genetics
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Research Support, Non-U.S. Gov't
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Transcription Factor AP-1/genetics/*physiology
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Transcription Factors/*genetics
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*Transcription, Genetic
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Up-Regulation
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Xenopus Proteins/*genetics
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Xenopus laevis/*embryology/*genetics