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Transcriptional regulatory elements in the long terminal repeats of the human endrogenous retrovirus, HERV-H Nelson, David Troy
Abstract
HERV-H sequences comprise a large family of human endogenous retroviruslike elements. Previous DNA sequence comparisons of HERV-H long terminal repeats (LTRs) have led to their classification into three subtypes, Type I, la and II. Type la appears to have been generated by recombination between Type I and II LTRs. These subtypes differ in evolutionary age and transcriptional activity with Type la LTRs being younger in evolutionary terms and possessing stronger promoter function than the other two subtypes. In this study, possible mechanics responsible for the functional difference between LTRs have been explored. Type I and II LTRs each contain different sets of repeated segments in their U3 regions which are disrupted in Type la LTRs. Using reporter gene assays, both types of repeated segments were shown to suppress activity of the human R-globin gene promoter when cloned at a distant site. Both sets of repeats also repress promoter activity of a Type la LTR when directly inserted within its U3 region. In further support of these findings, removal of the strongly supressing Type II repeat set from a Type II LTR increased promoter activity in one test cell line. However, this result was not observed in all cell lines or with both LTR types, emphasizing the complexity and cell-type dependence of HERV-H promoter regulation. In addition, using deletion constructs, two positive regulatory segments have been localized within the Type la LTR, both of which contain a potential binding site for the transcription factor Sp1. Gel mobility shift assays demonstrated that fragments containing these sites do bind Sp1. Although Type I LTRs are generally similar to Type la LTRs in the regions surrounding the Sp1 sites, there are sequence differences within the sites. Gel shift analysis revealed no, or much reduced, Sp1 binding of Type I LTR fragments containing these sites. Thus, it appears that the loss of repeated suppresser elements and the acquisition of Sp1 binding sites have both contributed to the relatively strong transcriptional activity of the Type la LTRs.
Item Metadata
Title |
Transcriptional regulatory elements in the long terminal repeats of the human endrogenous retrovirus, HERV-H
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1997
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Description |
HERV-H sequences comprise a large family of human endogenous retroviruslike
elements. Previous DNA sequence comparisons of HERV-H long terminal repeats
(LTRs) have led to their classification into three subtypes, Type I, la and II. Type la
appears to have been generated by recombination between Type I and II LTRs. These
subtypes differ in evolutionary age and transcriptional activity with Type la LTRs being
younger in evolutionary terms and possessing stronger promoter function than the
other two subtypes. In this study, possible mechanics responsible for the functional
difference between LTRs have been explored. Type I and II LTRs each contain
different sets of repeated segments in their U3 regions which are disrupted in Type la
LTRs. Using reporter gene assays, both types of repeated segments were shown to
suppress activity of the human R-globin gene promoter when cloned at a distant site.
Both sets of repeats also repress promoter activity of a Type la LTR when directly
inserted within its U3 region. In further support of these findings, removal of the
strongly supressing Type II repeat set from a Type II LTR increased promoter activity in
one test cell line. However, this result was not observed in all cell lines or with both
LTR types, emphasizing the complexity and cell-type dependence of HERV-H
promoter regulation. In addition, using deletion constructs, two positive regulatory
segments have been localized within the Type la LTR, both of which contain a
potential binding site for the transcription factor Sp1. Gel mobility shift assays
demonstrated that fragments containing these sites do bind Sp1. Although Type I
LTRs are generally similar to Type la LTRs in the regions surrounding the Sp1 sites,
there are sequence differences within the sites. Gel shift analysis revealed no, or
much reduced, Sp1 binding of Type I LTR fragments containing these sites. Thus, it
appears that the loss of repeated suppresser elements and the acquisition of Sp1
binding sites have both contributed to the relatively strong transcriptional activity of the
Type la LTRs.
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Extent |
5426820 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-03-25
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0088264
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1997-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.