The LTR enhancer of ERV-9 human endogenous retrovirus is active in oocytes and progenitor cells in transgenic zebrafish and humans
- Wenhu Pi*,
- Zhongan Yang†,‡,
- Jian Wang†,§,
- Ling Ruan†,
- Xiuping Yu*,
- Jianhua Ling*,
- Sanford Krantz¶,
- Carlos Isales†,∥,
- Simon J. Conway†,§,
- Shuo Lin†,‡, and
- Dorothy Tuan*,**
- *Department of Biochemistry and Molecular Biology and †Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912; ¶Division of Hematology and Oncology, Department of Medicine, Vanderbilt University and Veterans Affairs Medical Center, Nashville, TN 37232; and ∥Augusta Veterans Affairs Medical Center, Augusta, GA 30904
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Communicated by Irving M. London, Massachusetts Institute of Technology, Cambridge, MA, December 2, 2003 (received for review July 3, 2003)
Abstract
The solitary LTRs of ERV-9 human endogenous retrovirus are middle repetitive DNAs associated with 3,000–4,000 human gene loci including the β-globin gene locus where the ERV-9 LTR is juxtaposed to the locus control region (β-LCR) far upstream of the globin genes. The ERV-9 LTRs are conserved during primate evolution, but their function in the primate genomes is unknown. Here, we show that in transgenic zebrafish harboring the β-globin ERV-9 LTR coupled to the GFP gene, the LTR enhancer was active and initiated synthesis of GFP mRNA in oocytes but not in spermatozoa, and GFP expression in the embryos was maternally inherited. The LTR enhancer was active also in stem/progenitor cell regions of adult tissues of transgenic zebrafish. In human tissues, ERV-9 LTR enhancer was active also in oocytes and stem/progenitor cells but not in spermatozoa and a number of differentiated, adult somatic cells. Transcriptional analyses of the human β-globin gene locus showed that the β-globin ERV-9 LTR enhancer initiated RNA synthesis from the LTR in the direction of the downstream β locus control region and globin genes in ovary and erythroid progenitor cells. The findings suggest that, during oogenesis, ERV-9 LTR enhancers in the human genome could activate the cis-linked gene loci to synthesize maternal mRNAs required for early embryogenesis. Alternatively, the ERV-9 LTR enhancers, in initiating RNA syntheses into the downstream genomic DNAs, could transcriptionally potentiate and preset chromatin structure of the cis-linked gene loci in oocytes and adult stem/progenitor cells.
Footnotes
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↵ ** To whom correspondence should be addressed. E-mail: dtuanlo{at}mail.mcg.edu.
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↵ ‡ Present address: Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095.
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↵ § Present address: Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202.
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Abbreviations: LCR, locus control region; Tg, transgenic.
- Copyright © 2004, The National Academy of Sciences
