Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Long terminal repeats”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 703 records · Page 39Linked to original sources
PubMed1989

Polyadenylation function and sequence variability of the long terminal repeats of the human endogenous retrovirus-like family RTVL-H.

The RTVL-H family of human endogenous retrovirus-like sequences consists of approximately 1000 "full-length" elements and at least as many solitary RTVL-H related long terminal repeats (LTRs). We have characterized cDNA clones from two human cell libraries (Hep-2 and normal peripheral blood) and have found three clones in which the AATAAA signal within the RTVL-H LTR has functioned to polyadenylate the transcript. In two of these cases the LTR has provided the polyadenylation signal for non-RTVL-H initiated transcriptional units. The DNA sequences of the LTR regions from these three cDNA clones are significantly different from a consensus LTR sequence generated from 10 genomic LTRs. In fact, two of these cDNA-derived LTRs, although closely related to each other, have a subregion within them which is not found in the genomic LTRs that have been analyzed. LTRs containing this subregion, termed type II LTRs, comprise approximately 25% of the total genomic LTR population. In stable DNA transfection experiments, both a type I and a type II LTR were able to donate a functional polyadenylation signal to a neomycin resistance gene. In LTR-positive placental cDNA clones, type II LTRs were found more frequently than expected from their genomic abundance. These findings suggest that RTVL-H LTRs may provide 3' processing signals for a variety of human RNAs. They also indicate that at least one distinct subpopulation of RTVL-H LTRs can be distinguished and suggest that this or other subpopulations may have different functional capacities in different human cells.

Base Sequence↗
PubMed1989

Negative regulatory element associated with potentially functional promoter and enhancer elements in the long terminal repeats of endogenous murine leukemia virus-related proviral sequences.

Three series of recombinant DNA clones were constructed, with the bacterial chloramphenicol acetyltransferase (CAT) gene as a quantitative indicator, to examine the activities of promoter and enhancer sequence elements in the 5' long terminal repeat (LTR) of murine leukemia virus (MuLV)-related proviral sequences isolated from the mouse genome. Transient CAT expression was determined in mouse NIH 3T3, human HT1080, and mink CCL64 cultured cells transfected with the LTR-CAT constructs. The 700-base-pair (bp) LTRs of three polytropic MuLV-related proviral clones and the 750-bp LTRs of four modified polytropic proviral clones, in complete structures either with or without the adjacent downstream sequences, all showed very little or negligible activities for CAT expression, while ecotropic MuLV LTRs were highly active. The MuLV-related LTRs were divided into three portions and examined separately. The 3' portion of the MuLV-related LTRs that contains the CCAAC and TATAA boxes was found to be a functional promoter, being about one-half to one-third as active as the corresponding portion of ecotropic MuLV LTRs. A MboI-Bg/II fragment, representing the distinct 190- to 200-bp inserted segment in the middle, was found to be a potential enhancer, especially when examined in combination with the simian virus 40 promoter in CCL64 cells. A PstI-MboI fragment of the 5' portion, which contains the protein-binding motifs of the enhancer segment as well as the upstream LTR sequences, showed moderate enhancer activities in CCL6 cells but was virtually inactive in NIH 3T3 cells and HT1080 cells; addition of this fragment to the ecotropic LTR-CAT constructs depressed CAT expression. Further analyses using chimeric LTR constructs located the presence of a strong negative regulatory element within the region containing the 5' portion of the enhancer and the immediate upstream sequences in the MuLV-related LTRs.

Animals↗
PubMed1992

Transcriptional interaction between retroviral long terminal repeats (LTRs): mechanism of 5' LTR suppression and 3' LTR promoter activation of c-myc in avian B-cell lymphomas.

Chicken syncytial viruses induce bursal lymphomas by integrating into the c-myc locus and activating myc expression by 3' long terminal repeat (LTR) promoter insertion. In contrast to wild-type proviruses, in which transcription initiates predominantly in the 5'LTR, these myc-associated proviruses exhibit a predominance of transcription from the 3' LTR and little transcription from the 5' LTR. Most of these proviruses contain deletions within the 5' end of their genome that spare the 5' LTR. We report the identification of a 0.3-kb viral leader sequence that modulates 5' and 3' LTR transcriptional activities. In the presence of this sequence, transcription from the 5' LTR predominates, but in its absence, the 3' LTR promoter becomes activated, resulting in a high level of myc expression. This viral sequence does not behave like a classical enhancer; it activates transcription only when located downstream from the promoter and in the sense orientation. In this regard, it resembles the recently described human immunodeficiency virus RNA enhancer. This study suggests that retroviruses contain internal sequences which directionally activate the 5' LTR promoter to facilitate transcription of the viral genome and that deletion of these sequences is one step in the activation of the 3' LTR of myc-associated proviruses in avian bursal lymphomas.

Animals↗
PubMed2002

Differential requirements for activation of integrated and transiently transfected human T-cell leukemia virus type 1 long terminal repeat.

Adult T-cell leukemia (ATL) cells contain integrated human T-cell leukemia virus type 1 (HTLV-1) proviruses. Although the exact sequence of events leading to the development of ATL remains incompletely resolved, expression of the integrated HTLV-1 long terminal repeat (LTR) is likely required at some point during the process of T-cell transformation. While much has been learned about the regulated expression of transiently transfected LTR reporter plasmids, an analysis of factors required for expression of chromosomally integrated HTLV-1 LTR has not been done. Here, we have constructed CHOK1 and HeLa cells that contain an integrated HTLV-1 LTR-luciferase gene. Using these cells, we have compared the requirements for activation of transiently transfected versus stably integrated HTLV-1 LTR. We observed different requirements for CREB, p300, and P/CAF in the expression of transiently transfected versus stably integrated HTLV-1 LTR. Furthermore, with dominant-negative mutants of CREB, p300, and P/CAF, we found that activation of integrated HTLV-1 LTR by an ambient stress signal, UV-C, proceeds through a path mechanistically distinct from that used by viral oncoprotein, Tax. Our findings point to additional complexities in the regulated expression of HTLV-1 proviruses compared with those hitherto revealed through transfection studies.

Acetyltransferases↗
PubMed1999

The presence or absence of a retroviral long terminal repeat influences the genetic risk for type 1 diabetes conferred by human leukocyte antigen DQ haplotypes. Belgian Diabetes Registry.

Major genetic susceptibility to type 1 diabetes mellitus maps to the human leukocyte antigen (HLA) region on chromosome 6p. During evolution, endogenous retroviral long terminal repeats (LTR) have been integrated at several sites within this region. We analyzed the presence of a solitary HERV-K LTR in the HLA DQ region (DQ-LTR3) and its linkage to DRB1, DQA1, and DQB1 haplotypes derived from 246 German and Belgian families with a patient suffering from type 1 diabetes mellitus. Segregation analysis of 984 HLA DQA1/B1 haplotypes showed that DQ-LTR3 is linked to distinct DQA1 and DQB1 haplotypes but is absent in others. The presence of DQ-LTR3 on HLA DQB1*0302 haplotypes was preferentially transmitted to patients from heterozygous parents (82%; P < 10(-6)), in contrast to only 2 of 7 DQB1*0302 haplotypes without DQ-LTR3. Also, the extended HLA DRB1*0401, DQB1*0302 DQ-LTR3-positive haplotypes were preferentially transmitted (84%; P < 10(-6)) compared with 1 of 6 DR-DQ matched DQ-LTR3 negative haplotypes. DQ-LTR3 is missing on most DQB1*0201 haplotypes, and those LTR3 negative haplotypes were also preferentially transmitted to patients (80%; P < 10(-6)), whereas DQB1*0201 DQ-LTR3-positive haplotypes were less often transmitted to patients (36%). Other DQA1/B1 haplotypes did not differ for DQ-LTR3 between transmitted and nontransmitted haplotypes. Thus, the presence of DQLTR3 on HLA DQB1*0302 and its absence on DQB1*0201 haplotypes are independent genetic risk markers for type 1 diabetes.

Diabetes Mellitus, Type 1↗
PubMed1987

Mechanism of dexamethasone 21-mesylate antiglucocorticoid action: II. Receptor-antiglucocorticoid complexes do not interact productively with mouse mammary tumor virus long terminal repeat chromatin.

We have studied the interaction of covalent dexamethasone 21-mesylate (DM) labeled, activated glucocorticoid receptor with mouse mammary tumor virus (MMTV) chromatin. Studies were performed on a murine cell line (904.13) which contains 200 copies per cell of a MMTV long terminal repeat (LTR) v-rasH casette mobilized on bovine papilloma virus based episomes. DM binds covalently to glucocorticoid receptors and displays almost full antagonist activity in this cell line. In situ transcription extension assays indicate that activated receptor-DM complex cannot stimulate LTR-initiated transcription. The receptor-DM complex also fails to induce DNase I hypersensitivity (HSR) and transcription factor loading at the MMTV promoter. Transcription activation, HSR formation, and factor binding induced with the agonist dexamethasone are blocked by covalent occupation of the receptor by DM. Although DM-activated receptor binds specifically to receptor sites on purified LTR DNA, the antagonist receptor complex does not interact productively with MMTV LTR chromatin in vivo.

Animals↗
PubMed2026

Heat-responsive ONSEN long terminal repeats integrate heat shock factor motifs, DNA methylation and natural sequence variation in Arabidopsis.

ONSEN is a heat-activated Ty1/copia retrotransposon in Arabidopsis thaliana controlled by heat shock factors (HSFs) and epigenetic silencing. Heat shock element (HSE)-like sequences in ONSEN long terminal repeats (LTRs) contribute to heat responsiveness, but relationships among sequence architecture, basal DNA methylation and natural variation remain unclear. We combined transcription-factor motif prediction, transposable-element comparisons, methylome and RNA sequencing (RNA-seq) data, and Arabidopsis genome assemblies. In silico disruption of five HSE cores eliminated HSF-family motif compatibility in the selected design and all 5119 exact-guanine-cytosine (GC) alternatives. Across 16 curated Columbia-0 terminal windows, ONSEN contained 33-49 non-redundant HSF motif-coordinate placements per 800&#xa0;bp window and was strongly enriched relative to 1930 non-ONSEN transposable elements across score thresholds and continuous metrics. Direct comparison with 779 non-ONSEN LTR retrotransposons showed selectively elevated basal CHH methylation (where H = A, C or T) at ONSEN termini. Genome-wide RNA-seq analysis revealed broad heat-responsive gene and transposable-element changes, including strong ONSEN induction, whereas candidate-window analysis distinguished ONSEN from most HSF-rich non-ONSEN outliers. ONSEN-like variants across eight accessions generally retained HSF-compatible motifs while altering predicted DNA binding with one finger-family motif composition. Together, these findings define ONSEN terminal regions as HSF-rich regulatory sequences that retain heat-responsive potential within a methylated chromatin context and identify candidates for functional analysis.

DNA Methylation↗
PubMed1992

Biochemical analysis of the mouse mammary tumor virus long terminal repeat product. Evidence for the molecular structure of an endogenous superantigen.

Recent reports have shown that both exogenous and endogenous mouse mammary tumor viruses (MMTV) can encode superantigens. Transfection and transgenic studies have identified the open reading frame (ORF) present in the 3' long terminal repeat (LTR) as encoding superantigen function. In this study, we have used an in vitro translation system in an attempt to characterize the molecular nature of the protein encoded by the 3' ORF of Mtv-8. Using various constructs encoding full-length and truncated versions of the ORF product, we report that the hydrophobic region close to the amino terminus of the 36-kDa protein can function as a transmembrane domain. Protease digestion experiments also demonstrate that the protein has a type-II transmembrane conformation with an extra-cytoplasmic carboxy terminus. Since this hydrophobic region is conserved between all known MMTV, we speculate that LTR ORF, including those proposed to encode the minor lymphocyte stimulatory antigens, are also capable of encoding type-II transmembrane glycoproteins. The polymorphism between MMTV LTR ORF products, which correlates with deletion phenotypes, is predominantly in the carboxy-terminal extracellular region, consistent with a major role in interaction with the T cell receptor.

Animals↗
PubMed1985

The promoter of the long terminal repeat of feline leukemia virus is effective for expression of a mouse H-2 histocompatibility gene in mouse and human cells.

DNA-mediated gene transfer techniques have been used to study the effectiveness of a novel construction involving the feline leukemia virus long terminal repeat (FeLV LTR) for expressing the mouse H-2 Ld gene in mouse and human cells. In this construction, the transcription initiation (promoter) and termination (polyadenylation) functions of the FeLV LTR have been split by insertion of a promoterless H-2 gene between them. An S1 nuclease assay has been developed that makes it possible to measure accumulated LdRNA against a background of endogenous major histocompatibility antigen RNAs in mouse and human cells. In mouse cells, the H-2 Ld gene was expressed at approximately equal levels (measured as accumulated RNA) when driven either by its own promoter or by the FeLV LTR construction. In human cells, expression at the RNA level was highest when driven by the FeLV LTR. We conclude that the FeLV LTR construction is useful for expressing foreign genes in human cells.

Animals↗
PubMed1986

Two elements in the bovine leukemia virus long terminal repeat that regulate gene expression.

The bovine leukemia virus, like the human T-cell leukemia viruses (HTLV-I and HTLV-II), are unusual biologically in that viral transcripts are not detected in tumors or infected tissues. The bovine leukemia virus long terminal repeat (BLV LTR) functions as a transcriptional promoter only in cell lines productively infected with BLV. Deletion mapping indicated that at least two regions of the LTR, on the 5' and 3' sides of the RNA start site, influenced gene expression. An analysis has now been made of the effects of coupling sequences from these LTR regions to a heterologous core promoter derived from the SV40 early promoter unit. Through the use of the transient expression of the bacterial chloramphenicol acetyltransferase (CAT) gene to monitor transcriptional activity in vivo, two independent, regulatory elements were identified in the BLV LTR. One was present in a fragment of 75 base pairs derived from the U3 region of the LTR and behaved much like other enhancer elements. It may be a major determinant of BLV expression in productively infected cell lines, since it enhanced transcription controlled by the heterologous core promoter only in these cells. The second element was contained in a 250-bp fragment derived from LTR sequences in the R region, located downstream from the RNA start site. Its activation of CAT expression was not dependent on BLV infection and was evident only when the fragment was located immediately downstream from the RNA start site. BLV expression thus appears to be regulated in part by a cell-specific enhancer element upstream from the core promoter and a novel sequence downstream from the RNA initiation site in the viral LTR.

Animals↗
PubMed1987

Sequences responsible for erythroid and lymphoid leukemia in the long terminal repeats of Friend-mink cell focus-forming and Moloney murine leukemia viruses.

Despite the high degree of homology (91%) between the nucleotide sequences of the Friend-mink cell focus-forming (MCF) and the Moloney murine leukemia virus (MuLV) genomic long terminal repeats (LTRs), the pathogenicities determined by the LTR sequences of the two viruses are quite different. Friend-MCF MuLV is an erythroid leukemia virus, and Moloney MuLV is a lymphoid leukemia virus. To map the LTR sequences responsible for the different disease specificities, we constructed nine viruses with LTRs recombinant between the Friend-MCF and Moloney MuLVs. Analysis of the leukemia induced with the recombinant viruses showed that a 195-base-pair nucleotide sequence, including a 75-base-pair nucleotide Moloney enhancer, is responsible for the tissue-specific leukemogenicity of Moloney MuLV. However, not only the enhancer but also its downstream sequences appear to be necessary. The Moloney virus enhancer and its downstream sequence exerted a dominant effect over that of the Friend-MCF virus, but the enhancer sequence alone did not. The results that three of the nine recombinant viruses induced both erythroid and lymphoid leukemias supported the hypothesis that multiple viral genetic determinants control both the ability to cause leukemia and the type of leukemia induced.

Animals↗
PubMed1986

Bidirectional transcription from a solo long terminal repeat of the retrotransposon TED: symmetrical RNA start sites.

A single copy of the retrotransposon TED was found integrated within the DNA genome of the insect baculovirus, Autographa californica nuclear polyhedrosis virus. After excision of the element from the viral genome, a single long terminal repeat (LTR) remained behind. We have examined the effect of this solo TED LTR on the local pattern of viral transcription. Most prominent was the transcription of two sets of abundant RNAs; both originated within the LTR but extended in opposite directions into flanking viral genes. By promoting symmetric transcription of adjacent genes, the solo LTR has the capacity to activate or repress gene expression in two directions. Primer extension analysis demonstrated that the divergent LTR transcripts were initiated near the same point within a 22-base-pair sequence having hyphenated twofold symmetry. Analogous symmetries at the initiation sites of other retrotransposon LTRs, including copia and Ty, suggested that these sequences serve to establish the precise start for transcription.

Animals↗
PubMed1999

Two point mutations in the U3 region of the long terminal repeat convert a subgroup A transformation-defective rous sarcoma virus to a cytopathic virus.

To elucidate the mechanism of cytopathicity of the transformation-defective avian retrovirus tdPH2010, we examined the function of two point mutations we had previously found in the long terminal repeat U3 region of this virus. Our previous studies showed that the U3 region was responsible for the cytopathic effects. These mutations were a G-to-T mutation at position -126 from the transcription start site and a G-to-A mutation at -23. Site-directed mutagenesis was performed on a noncytopathic, wild-type virus BSU to alter the nucleotides at these two positions, one at a time, to those of tdPH2010. Cell growth assay using the altered viruses revealed that host cell growth was retarded only when both of these mutations were present. The two additional mutations previously found in the direct repeat 1-polypurine tract (DR1-PPT) region of tdPH2010 were present also in the noncytopathic strain tdPH2013. Site-directed mutagenesis confirmed that these two mutations had indeed no role in the cytopathic effect of tdPH2010. None of these mutations influenced virus production from the infected cells. We conclude that the cytopathic effects by tdPH2010 are ascribed to the two point mutations in the U3 region.

Animals↗
PubMed1980

Identification of a functional promoter in the long terminal repeat of Rous sarcoma virus.

Specific initiation of transcription of Rous sarcoma virus by RNA polymerase II was obtained in a cell-free system using cloned RSV DNA as template. The site of initiation is located in the common "C" region of the long terminal repeat (LTR), 23 bp downstream from the promoter-like sequence TATTTAAG. This finding indicates that the basic information necessary for RSV transcription lies within the viral genome.

Adenoviruses, Human↗
PubMed1985

Circles with two tandem long terminal repeats are specifically cleaved by pol gene-associated endonuclease from avian sarcoma and leukosis viruses: nucleotide sequences required for site-specific cleavage.

The avian retroviral pol gene-encoded DNA endonuclease (pol-endo) has been shown to selectively cleave the viral long terminal repeat sequences (LTRs) in single-stranded DNA substrates in a region known to be joined to host DNA during integration (G. Duyk, J. Leis, M. Longiaru, and A.M. Skalka, Proc. Natl. Acad. Sci. USA 80:6745-6749, 1983). The preferred sites of cleavage were mapped to the unique U5/U3 junctions found only in covalently closed circular DNA molecules containing two tandem LTRs. The cuts occurred three nucleotides 5' to the axis of symmetry of the 12-of-15-base-pair nearly perfect inverted repeat which marks the LTR junction. Experiments with double-stranded supercoiled DNA substrates revealed a similar specificity for nicking. Also, the endonuclease associated with the pol cleavage product, pp32, has the same specificity as the alpha beta form. The limits of sequence required for site-selective cleavage near the U5/U3 junction were established with single-stranded DNA substrates. A domain no larger than 44 base pairs allowed site-selective cleavage in each strand in vitro. Recognition of either strand appeared to be independent of the other, and in each case, the critical sequence was asymmetrically distributed with respect to the U5/U3 junction. The predominant contribution was from the U5 domain; this is consistent with its conservation in the LTR sequences of a number of avian sarcoma and leukosis viruses.

Alpharetrovirus↗
PubMed1991

Sequence-specific interaction of the Ets1 protein with the long terminal repeat of the human T-lymphotropic virus type I.

We recently demonstrated that members of the c-ets proto-oncogene family, Ets1 and Ets2, are sequence-specific transcriptional activators of the human T-lymphotropic virus type I (HTLV-I) long terminal repeat (LTR). We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2. Expression of Ets1 with reporter plasmids containing ERR-1 or ERR-2 upstream of a basal promoter resulted in an increase in transcriptional activity. By gel mobility shift assay, the interaction of Ets1 with the downstream ERR-1-binding region was found to be more stable than its interaction with the upstream ERR-2 region. By DNase I footprint, gel mobility shift, and methylation interference analyses, ERR-1 was found to contain two Ets1 binding sites, ERE-A and ERE-B. A recombinant Ets1 protein was found to bind with higher affinity to ERE-A than to ERE-B. Binding of Ets1 to these sites appears to result in a specific and sequential protection of a 37-nucleotide sequence of the HTLV-I LTR from -154 to -118. In view of the high-level expression of Ets1 in lymphoid cells, the c-ets proto-oncogenes encode transcription factors which could play an important role in both basal and Tax1-mediated HTLV-I transcription.

Animals↗
PubMed1986

Diverse long terminal repeats are associated with murine retroviruslike (VL30) elements.

The VL30 family is a retroviruslike gene family with no apparent nucleic acid homology to any known retrovirus. Over 100 copies of VL30 DNA elements are dispersed throughout the mouse genome. Sequence analysis of the VL30 long terminal repeat (LTR) units showed that, whereas the LTR units of a given VL30 DNA element were almost identical, the LTR units associated with distinct members of the family were very different from one another. Comparison of the LTR sequences possessed by two particular VL30 DNA elements revealed a pattern of extensively homologous DNA segments adjacent to only distantly related DNA sequences. With the aid of sub-LTR probes, it was shown that a certain LTR is composed of both U5 sequences that are abundantly present in all species of the genus Mus and a U3 region detected only in Mus musculus. In addition, we isolated a VL30 DNA element in which the LTR units were replaced by the LTR units of an apparently novel retroviruslike family. These findings suggest that recombinations have played a role in generating the diverse population of VL30-associated LTRs.

Animals↗
PubMed1995

Complement component C4 gene intron 9 as a phylogenetic marker for primates: long terminal repeats of the endogenous retrovirus ERV-K(C4) are a molecular clock of evolution.

The complement component C4 genes of Old World primates exhibit a long/short dichotomous size variation, except that chimpanzee and gorilla only contain short C4 genes. In human it has been shown that the long C4 gene is attributed to the integration of an endogenous retrovirus, HERV-K(C4), into intron 9. This 6.36 kilobase retroviral element is absent in short C4 genes. Here it is shown that the homologous endogenous retrovirus, ERV-K(C4), is present precisely at the same position in the long C4 gene of orangutan and African green monkey. Determination of the short C4 gene intron 9 sequences from human, three apes, two Old World monkeys, and a New World monkey allowed the establishment of consistent phylogenetic trees for primates, which favors a chimpanzee-gorilla clade. The 5' long terminal repeats (LTR) and 3' LTR of ERV-K(C4) in long C4 genes of human, orangutan, and African green monkey have similar sequence divergence values of 9.1%-10.5%. These values are more than five-fold higher than the sequence divergence of the homologous intron 9 sequences between the long and short C4 genes in higher primates. The latter is probably a result of homogenization or concerted evolution. We suggest that the 5' LTR and 3' LTR of an endogenous retrovirus can serve as a reliable reference point or a molecular clock for studies of gene duplication and gene evolution. This is because the 5'/3' LTR sequences were identical at the time of retroviral integration and evolved independently of each other afterwards. Our data provides strong evidence for the short C4 gene being the ancestral form in primates, trans-species evolution, and the "slow-down" phenomenon of the sequence divergence in great apes.

Amino Acid Sequence↗