Transcriptional regulation of Zic3 by heterodimeric AP-1(c-Jun/c-Fos) during Xenopus development.
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.
Lee
Sung-Young
SY
Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Kangwon-do 200-702, Korea.
Lee
Hyun-Shik
HS
Moon
Jin-Soo
JS
Kim
Jong-Il
JI
Park
Jae-Bong
JB
Lee
Jae-Yong
JY
Park
Mae Ja
MJ
Kim
Jaebong
J
D028341:Activins / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016384:Consensus Sequence / Q000235:genetics; D019281:Dimerization; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology; D016372:RNA, Antisense / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D015854:Up-Regulation; D029867:Xenopus Proteins / Q000235:genetics*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics*
D018398:Homeodomain Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016372:RNA, Antisense; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D029867:Xenopus Proteins; C109036:Zic3 protein, Xenopus; D028341:Activins