Direct repeats located within a large family of human endogenous retroviral LTRs have transcriptional suppressor activity in human cells
- Univ. of British Columbia, Vancouver (Canada)
The human genome harbors thousands of sequences that resemble retroviral long terminal repeats (LTRs). These LTR-like elements are associated with full length endogenous retroviral sequences and can also be found as solitary units. Since the U3 regions of retroviral LTRs contain transcriptional regulatory sequences, we have been interested in determining how the presence of endogenous LTRs may affect adjacent gene expression. One endogenous retroviral family, termed HERV-H, has {approximately}1000 copies per haploid genome in addition to {approximately}1000 solitary LTRs. HERV-H LTRs can be grouped into 3 subtypes that vary greatly in their promoter and enhancer activity. The primary feature that distinguishes the 3 LTR subtypes is the sequence of direct repeats located in U3. The most numerous LTR subtype, type 1, has 2 copies of a 47 bp repeat while the next most abundant type, type 2, usually has 5 copies of a different 31 bp repeat. The transcriptional activity of both type 1 and 2 LTRs is limited compared to the activity of a less abundant third subtype, type 1a, which is a much stronger promoter. Type 1a LTRs appear to be a recombinant between types 1 and 2, having only a single type 1 and a single type 2 repeat. In this study, we have analyzed type 1 and 2 repeats for enhancer or suppressor function. Using transient expression of a reporter gene, we have found that a set of type 2 repeats suppresses activity of a type 1a LTR promoter and the human {beta}-globulin promoter. Two sets of the type 1 repeat also have a suppressor effect. Thus, it is possible that type 1 and 2 LTRs in the genome could suppress the expression of nearby genes. Interestingly, HERV-H elements with type 1a LTRs appeared most recently in evolution, being restricted to the great apes and humans. These results suggest that disruption of the repeat structure in type 1a LTRs may be at least partially responsible for their strong promoter activity and their resultant genomic expansion.
- OSTI ID:
- 133854
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0588
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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