Transcription of two human genes from a bidirectional endogenous retrovirus promoter.
Eight percent of the human genome is derived from endogenous retrovirus (ERV) insertions. ERV long terminal repeats (LTRs) contain strong promoters that are known to contribute to the transcriptional regulation of certain human genes. While some LTRs are known to possess bidirectional promoter activity in vitro, only sense orientation LTR promoters have previously been shown to regulate human gene expression. Here we demonstrate that an ERV1 LTR acts as a bidirectional promoter for the human Down syndrome critical region 4 (DSCR4) and DSCR8 genes. We show that while DSCR4 and DSCR8 are essentially co-expressed, their shared LTR promoter is more active in the sense than the antisense orientation. Through deletion analysis of the LTR we have identified positive and negative regulatory elements, and defined a core region of the promoter that is required for transcriptional activity in both orientations. Finally, we show that the ERV LTR also exists in the genomes of several non-human primates, and present evidence that potential transcription factor binding sites in the core region have been maintained throughout primate evolution.
Dunn
Catherine A
CA
Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3.
Romanish
Mark T
MT
Gutierrez
Leanne E
LE
van de Lagemaat
Louie N
LN
Mager
Dixie L
DL
D000951:Antigens, Neoplasm / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D004314:Down Syndrome / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D011257:Pregnancy Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D062085:RNA, Long Noncoding; D012190:Retroviridae / Q000235:genetics; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*
D000951:Antigens, Neoplasm; C110524:DSCR4 lncRNA, human; C453740:DSCR8 lncRNA, human; D011257:Pregnancy Proteins; D062085:RNA, Long Noncoding