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Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes.

ABSTRACT: In the human genome, retrotranspositionally competent long interspersed nuclear elements (L1Hs) are involved in the generation of processed pseudogenes and mobilization of unrelated sequences into existing genes. Transcription of each L1Hs is initiated from its internal promoter but may also be driven from the promoters of adjacent cellular genes. Here I show that a hitherto unknown L1Hs antisense promoter (ASP) drives the transcription of adjacent genes. The ASP is located in the L1Hs 5' untranslated region (5'UTR) and works in the opposite direction. Fifteen cDNAs, isolated from a human NTera2D1 cDNA library by a differential screening method, contained L1Hs 5'UTRs spliced to the sequences of known genes or non-proteincoding sequences. Four of these chimeric transcripts, selected for detailed analysis, were detected in total RNA of different cell lines. Their abundance accounted for roughly 1 to 500% of the transcripts of four known genes, suggesting a large variation in the efficiency of L1Hs ASP-driven transcription. ASP-directed transcription was also revealed from expressed sequence tag sequences and confirmed by using an RNA dot blot analysis. Nine of the 15 randomly selected genomic L1Hs 5'UTRs had ASP activities about 7- to 50-fold higher than background in transient transfection assays. ASP was assigned to the L1Hs 5'UTR between nucleotides 400 to 600 by deletion and mutation analysis. These results indicate that many L1Hs contain active ASPs which are capable of interfering with normal gene expression, and this type of transcriptional control may be widespread.

SUBMITTER: Speek M

PROVIDER: S-EPMC86790 | biostudies-literature | 2001 Mar

REPOSITORIES: biostudies-literature

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Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes.

Speek M M

Molecular and cellular biology 20010301 6

In the human genome, retrotranspositionally competent long interspersed nuclear elements (L1Hs) are involved in the generation of processed pseudogenes and mobilization of unrelated sequences into existing genes. Transcription of each L1Hs is initiated from its internal promoter but may also be driven from the promoters of adjacent cellular genes. Here I show that a hitherto unknown L1Hs antisense promoter (ASP) drives the transcription of adjacent genes. The ASP is located in the L1Hs 5' untran ...[more]

PMID: 11238933

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Project description:The region of the human cytomegalovirus (HCMV) genome between the UL127 promoter and the major immediate-early (MIE) enhancer is referred to as the unique region. The role of this region during a viral infection is not known. In wild-type HCMV-infected permissive fibroblasts, there is no transcription from the UL127 promoter at any time during productive infection. Our investigators previously reported that the region upstream of the UL127 TATA box repressed expression from the UL127 promoter (C. A. Lundquist et al., J. Virol. 73:9039-9052, 1999). The region was reported to contain functional NF1 DNA binding sites (L. Hennighausen and B. Fleckenstein, EMBO J. 5:1367-1371, 1986). Sequence analysis of this region detected additional consensus binding sites for three transcriptional regulatory proteins, FoxA (HNF-3), suppressor of Hairy wing, and CAAT displacement protein. The cis-acting elements in the unique region prevented activation of the early UL127 promoter by the HCMV MIE proteins. In contrast, deletion of the region permitted very high activation of the UL127 promoter by the viral MIE proteins. Mutation of the NF1 sites had no effect on the basal activity of the promoter. To determine the role of the other sites in the context of the viral genome, recombinant viruses were generated in which each putative repressor site was mutated and the effect on the UL127 promoter was analyzed. Mutation of the putative Fox-like site resulted in a significant increase in expression from the viral early UL127 promoter. Insertion of wild-type Fox-like sites between the HCMV immediate-early (IE) US3 TATA box and the upstream NF-kappaB-responsive enhancer (R2) also significantly decreased gene expression, but mutated Fox-like sites did not. The wild-type Fox-like site inhibits activation of a viral IE enhancer-containing promoter. Cellular protein, which is present in uninfected or infected permissive cell nuclear extracts, binds to the wild-type Fox-like site but not to mutated sites. Reasons for repression of UL127 gene transcription during productive infection are discussed.

Dataset Information

Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes.

Publications

Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes.

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