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J Virol. 2006 Nov;80(21):10752-62.

At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo as active promoters for host nonrepetitive DNA transcription.

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1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia. anton@humgen.siobc.ras.ru

Abstract

We report the first genome-wide comparison of in vivo promoter activities of a group of human-specific endogenous retroviruses in healthy and cancerous germ line tissues. To this end, we employed a recently developed technique termed genomic repeat expression monitoring. We found that at least 50% of human-specific long terminal repeats (LTRs) possessed promoter activity, and many of them were up- or downregulated in a seminoma. Individual LTRs were expressed at markedly different levels, ranging from approximately 0.001 to approximately 3% of the housekeeping beta-actin gene transcript level. We demonstrated that the main factors affecting the LTR promoter activity were the LTR type (5'-proviral, 3' proviral, or solitary) and position with regard to genes. The averaged promoter strengths of solitary and 3'-proviral LTRs were almost identical in both tissues, whereas 5'-proviral LTRs displayed two- to fivefold higher promoter activities. The relative content of promoter-active LTRs in gene-rich regions was significantly higher than that in gene-poor loci. This content was maximal in those regions where LTRs "overlapped" readthrough transcripts. Although many promoter-active LTRs were mapped near known genes, no clear-cut correlation was observed between transcriptional activities of genes and neighboring LTRs. Our data also suggest a selective suppression of transcription for LTRs located in gene introns.

PMID:
17041225
PMCID:
PMC1641792
DOI:
10.1128/JVI.00871-06
[Indexed for MEDLINE]
Free PMC Article
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