Retrovirus-like promoters in the human genome
Several families of repetitive sequences related to integrated retroviruses have been identified in the human genome. The largest of these families, the RTVL-H family, has close to 1,000 members, in addition to several hundred solitary long terminal repeats (LTRs). The similarity of these LTRs in structure and organization to the LTRs of proviruses suggest that they may act as transcriptional regulators of gene expression. To test this hypothesis, the author initially examined the ability of different RTVL-H LTRs to drive expression of the reporter gene chloramphenicol acetyltransferase (CAT) in a variety of human and murine cell lines. These studies revealed that RTVL-H LTRs are heterogeneous in their ability to regulate the expression of linked genes. Although all of five LTRs tested could promote expression of the CAT gene, their relative promoter activities as well as range of activities varied widely. RTVL-H LTRs were also shown to contain sequences that could increase transcription from the human [beta]-globin promoter and be influenced by SV40 enhancer sequences. The results of additional studies suggested that RTVL-H LTRs may have the ability to influence the expression of unrelated cellular genes. Taken together, these results suggest a general evolutionary role for RTVL-H LTRs in the regulation of gene expression and raise the possibility that activation or rearrangements involving these sequences may alter the normal regulation of cellular genes and thus contribute to human disease.
- Research Organization:
- British Columbia Univ., Vancouver, BC (Canada)
- OSTI ID:
- 5607304
- Resource Relation:
- Other Information: Thesis (Ph.D.). Order No. DANN75469
- Country of Publication:
- United States
- Language:
- English
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