At least 50% of human-specific HERV-K (HML-2) long terminal repeats serve in vivo as active promoters for host nonrepetitive DNA transcription
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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DOI：
10.1128/jvi.00871-06
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Sverdlov, Eugene
中科院分区：
文献类型：
--
作者：
Buzdin, Anton;Kovalskaya-Alexandrova, Elena;Sverdlov, Eugene
我们报告了一组人类特异性内源逆转录病毒在健康和癌性种系组织中的体内启动子活性的首次全基因组比较。为此，我们采用了一种最近开发的技术，称为基因组重复表达监测。我们发现至少 50% 的人类特异性长末端重复序列 (LTR) 具有启动子活性，并且其中许多在精原细胞瘤中上调或下调。各个 LTR 的表达水平显着不同，范围从 0.001% 到 3% 不等。我们证明影响LTR启动子活性的主要因素是LTR类型（5'-原病毒、3'原病毒或单独）和基因位置。两种组织中单独LTR 和3'-原病毒LTR 的平均启动子强度几乎相同，而5'-原病毒LTR 显示出高出两到五倍的启动子活性。基因丰富区域中启动子活性LTR的相对含量显着高于基因贫乏区域。在 LTR“重叠”通读转录本的那些区域中，该内容最大。尽管许多启动子活性 LTR 被定位在已知基因附近，但在基因的转录活性和邻近 LTR 之间没有观察到明确的相关性。我们的数据还表明，位于基因内含子中的 LTR 的转录存在选择性抑制。
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 similar to 0.001 to similar to 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.