At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo as active promoters for host nonrepetitive DNA transcription.
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.
Buzdin
Anton
A
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia. anton@humgen.siobc.ras.ru
Kovalskaya-Alexandrova
Elena
E
Gogvadze
Elena
E
Sverdlov
Eugene
E
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D015723:Gene Library; D023281:Genomics; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D018239:Seminoma / Q000235:genetics / Q000821:virology; D020079:Terminal Repeat Sequences; D013736:Testicular Neoplasms / Q000235:genetics / Q000821:virology; D013737:Testis / Q000378:metabolism / Q000821:virology; D014158:Transcription, Genetic
D017931:DNA Primers; D004279:DNA, Viral