title: EZR1: a novel family of highly expressed retroelements induced by TCDD and regulated by a NF-κB-like factor in embryos of zebrafish (Danio rerio).
abstract: Transcript profiling using a zebrafish heart cDNA library previously revealed abundant expressed sequence tags (ESTs) upregulated in zebrafish embryos treated with the aryl hydrocarbon receptor (AHR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Here, we identify those ESTs as LTR-containing retroelements termed EZR1 (Expressed-Zebrafish-Retroelement group 1). EZR1 is highly redundant in the genome and includes canonical long terminal repeats (LTRs) flanking an integrase-like open reading frame and a region similar to retroviral envelope protein genes. EZR1 sequences lack reverse transcriptase, RNase H, or protease, indicating retrotransposition would be nonautonomous. No AHR binding motifs were found in the EZR1 promoter region. A putative NF-κB-binding site was found, and TCDD-treated zebrafish embryos had significantly increased levels of nuclear protein(s) binding to this sequence. Protein-EZR1 DNA complex formation was partially competed by a mammalian consensus κB sequence, consistent with NF-κB-like activation contributing to increased protein binding to this site. Mobility of the TCDD-induced protein-EZR1 complex differed from that of authentic NF-κB protein bound to the consensus κB site. The results suggest that EZR1 is regulated by interaction with NF-κB or NF-κB-like protein(s) different from the NF-κB protein binding to the consensus κB site. The nature of the NF-κB-like protein and the relationship between EZR1 induction and cardiovascular toxicity caused by TCDD warrant further investigation.
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Woods Hole, Massachusetts, USA.
authors.forename: Heather M H
authors.initials: HM
authors.lastname: Goldstone
authors.forename: Saimi
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Schlezinger
authors.forename: Jared V
authors.initials: JV
authors.lastname: Goldstone
authors.forename: John J
authors.initials: JJ
authors.lastname: Stegeman
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D010802:Phylogeny; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger; D018626:Retroelements / Q000235:genetics / Q000502:physiology*; D020079:Terminal Repeat Sequences; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018626:Retroelements; D029961:Zebrafish Proteins