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

J Virol. 2006 Nov;80(21):10752-62. doi: 10.1128/JVI.00871-06.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA Primers / genetics
  • DNA, Viral / genetics
  • Endogenous Retroviruses / genetics*
  • Gene Expression Regulation, Viral
  • Gene Library
  • Genomics
  • Humans
  • Male
  • Promoter Regions, Genetic*
  • Seminoma / genetics
  • Seminoma / virology
  • Terminal Repeat Sequences*
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / virology
  • Testis / metabolism
  • Testis / virology
  • Transcription, Genetic

Substances

  • DNA Primers
  • DNA, Viral