PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Long terminal repeats”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 1,027 records · Page 57Linked to original sources
PubMed1989

The human immunodeficiency virus long terminal repeat is preferentially expressed in Langerhans cells in transgenic mice.

Four lines of transgenic mice containing the HIV LTR linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT) were constructed. In each line, a characteristic tissue pattern of CAT expression was observed with detectable levels present in the eye, heart, spleen, thymus, and tail. Low levels of CAT were present in circulating lymphocytes, but CAT activity in these cells could be augmented following treatment with the mitogen phytohemagglutinin (PHA). Likewise, CAT expression was present at only low levels in circulating monocytes, but higher levels of CAT were observed in macrophages grown in the presence of various cytokines (CSF-1, GM-CSF, IL-1 alpha, IL-4, and IL-2). Furthermore, Langerhans cells recovered from skin showed higher levels of CAT activity than those observed in other cells of monocyte-macrophage lineage. These results indicate that LTR-CAT expression in cells of monocyte-macrophage lineage may increase in proportion to the degree of differentiation of these cells. These animals may be useful in the study of cell-specific determinants of LTR-directed gene activity and may serve to identify exogenous cofactors that promote the progression of HIV-related disease in vivo.

Animals↗
PubMed1993

Isolation of a cDNA clone encoding DNA-binding protein (TAXREB107) that binds specifically to domain C of the tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I.

Five cDNA clones for TAXREB proteins that bind to the tax-responsive enhancer element of human T-cell leukemia virus type I (HTLV-I) were isolated from a Jurkat cell cDNA library. The beta-galactosidase fusion proteins of three of these clones specifically recognized the domain C within the enhancer. One of the three cDNAs, encoding TAXREB107, contained an open reading frame with 288 amino acid residues. RNA blot analysis showed that the level of mRNA for TAXREB107 increased transiently in Jurkat cells on treatment with TPA. Immunoblot analysis showed that polyclonal antibody against TAXREB107 specifically recognized a 34-kD protein in Jurkat cells. TAXREB107 may participate in tax-mediated trans-activation of transcription.

Amino Acid Sequence↗
PubMed1998

Insertion of two independent enhancers in the long terminal repeat of a self-inactivating vector results in high-titer retroviral vectors with tissue-specific expression.

The use of retroviral vectors (RVs) derived from the murine oncoretroviruses for gene therapy is associated with the risk of malignant transformation of infected cells and ectopic expression of the proteins of interest. Targeting retroviral vectors to specific tissues would increase their safety and clinical applicability. To explore the potential of targeting vector expression to skeletal muscle, the murine leukemia virus broad transcriptional tropism was modified by substituting the viral promoter and/or enhancer with a transcriptional cassette containing the human T cell leukemia virus type I Tax-responsive element and the minimal muscle creatine kinase enhancer and promoter. The resulting retroviral vectors could be transcriptionally trans-activated by tax. In the absence of Tax, however, the viruses showed muscle-specific expression. Trans-complementing packaging and indicator cells stably expressing Tax were used to isolate high-titer producer cell clones (10(6) CFU/ml). In vitro, the levels of expression of these RVs in Tax-expressing fibroblasts were 10,000-fold higher than in normal fibroblasts and 1000-fold higher in C2C12 myotubes than in C2C12 myoblasts. Expression of the vectors and the endogenous muscle creatine kinase gene was similarly dependent on the maturity of the muscle cultures. One vector with modified LTRs was also tested in vivo in regenerating muscle and showed a delayed pattern of expression in myofibers compared with the vector containing the wild-type LTRs. These vectors can be easily modified to contain different tissue-specific enhancer and promoter elements and the availability of complementing packaging and indicator cells expressing Tax should allow their application in a variety of gene therapy settings.

3T3 Cells↗
PubMed2002

Dasheng: a recently amplified nonautonomous long terminal repeat element that is a major component of pericentromeric regions in rice.

A new and unusual family of LTR elements, Dasheng, has been discovered in the genome of Oryza sativa following database searches of approximately 100 Mb of rice genomic sequence and 78 Mb of BAC-end sequence information. With all of the cis-elements but none of the coding domains normally associated with retrotransposons (e.g., gag, pol), Dasheng is a novel nonautonomous LTR element with high copy number. Over half of the approximately 1000 Dasheng elements in the rice genome are full length (5.6-8.6 kb), and 60% are estimated to have amplified in the past 500,000 years. Using a modified AFLP technique called transposon display, 215 elements were mapped to all 12 rice chromosomes. Interestingly, more than half of the mapped elements are clustered in the heterochromatic regions around centromeres. The distribution pattern was further confirmed by FISH analysis. Despite clustering in heterochromatin, Dasheng elements are not nested, suggesting their potential value as molecular markers for these marker-poor regions. Taken together, Dasheng is one of the highest-copy-number LTR elements and one of the most recent elements to amplify in the rice genome.

Centromere↗
PubMed1983

A novel sequence segment and other nucleotide structural features in the long terminal repeat of a BALB/c mouse genomic leukemia virus-related DNA clone.

A recombinant DNA clone, named AL10, that contains murine leukemia virus (MuLV) related sequences was isolated from BALB/c mouse chromosomal DNA and examined in detail. Restriction endonuclease mapping revealed that the 10.5 kbp EcoRI insert consists of a 3.6 kbp left flanking cellular DNA region and a 6.9 kbp MuLV-related region that has a typical proviral LTR-gag-pol-env structure up to the EcoRI site in the env gene region. Comparison of the AL10 map with ecotropic and xenotropic virus isolates revealed many common restriction sites in the LTR and pol gene regions, but much fewer in the leader and gag regions. A stretch of 1,700 nucleotides containing the cellprovirus junctional region was sequenced and revealed transcriptional consensus signals and other structural features characteristic of MuLV LTRs, as well as two distinctive features: (a) a sequence of approximately 170 bp with direct and inverted terminal repeats not seen in infectious MuLV LTRs was identified in the U3 region between the "enhancer" region and the "CAT" box. This novel segment or its homologous sequences appear to be present in most of the endogenous MuLV-related LTRs and in other chromosomal locations of the mouse (b) The tRNA primer binding site is not complementary to proline tRNA, the primer for all known MuLVs, but is a 17/18 match with rat glutamine tRNA. The integration site of AL10 provirus was in a unique DNA region but contained an "Alu"-like short interdispersed repeat in the 5' adjacent cellular region. The AL10 proviral integration found in BALB/c was also apparent in RFM, AKR and SENCAR mouse cells but not in cells of NFS/N, C3H, HRS/J, SC-1, and a California Lake Casitas wild mouse.

Animals↗
PubMed1984

Nucleotide sequences of the retroviral long terminal repeats and their adjacent regions.

The nucleotide sequences of the LTRs and their adjacent regions from 19 type C and one type B retrovirus were compared. Salient features are: (a) The R regions in the genomes of most of the type C retroviruses begin with GC and end with CA. (b) The mammalian type C retroviruses have a polyadenylation signal "AATAAA" in the R region, and most have a "CAT" box and a "TATA" box in the U3 region. (c) The avian type C retroviruses have an AATAAA sequence, and some also have "CAT-like" and "TATA-like" boxes, in the U3 region. (d) As with many transposable elements, the IR regions of the proviruses begin with TG and end with CA, and the DR sequences in the host genomes flanking the proviruses are different from one another. Although SNV is an avian retrovirus, the nucleotide sequences in the R, U5, TBS, and PU region are more similar to the mammalian type C than to the avian type C retroviruses.

Animals↗
PubMed1985

Functional RNA polymerase II promoters in solitary retroviral long terminal repeats (LTR-IS elements).

LTR-IS elements are middle repetitive sequences in the mouse genome with structural features of solitary retroviral LTRs. In order to get some insight in the possible functional role of these sequences the promotor activity of two LTR-IS representatives differing by 105 bp in their U3 region was investigated. Gene fusions between LTR-IS sequences and the bacterial gene coding for chloramphenicol acetyl transferase (CAT) were transfected into mouse 3T6 cells and the expression of CAT was measured. It is shown that the LTR-IS sequences represent weak RNA polymerase II promoters which require enhancement by cis-or trans-activating factors.

Acetyltransferases↗
PubMed1986

Promoter and enhancer activities of long terminal repeats associated with cellular retrovirus-like (VL30) elements.

LTR units associated with cellular retrovirus-like elements are abundantly present in chromosomal DNA of animal cells. We have analyzed the promoter and enhancer activities of diverse LTR units associated with different members of the murine retrovirus-like family known as VL30. We report here that the structurally heterogenous VL30 LTRs displayed highly variable promoter/enhancer activities. The most active VL30 LTR (designated VL3) promoted CAT activity to levels six-fold higher than the LTR of the strongly transforming retrovirus, MSV. This VL30 transcription unit, containing a unique U3 region, was further characterized by S1 nuclease mapping. VL3 LTR functioned as an enhancer in CAT constructs containing a SV40 promoter. In addition, a defined U3 segment was shown to augment expression of CAT in an orientation independent manner. VL3 LTR also served as an efficient promoter and enhancer in heterologous monkey cells. These results suggest that certain resident LTRs possess promoter and enhancer capacities greater than those possessed by LTRs of infectious retroviruses.

Acetyltransferases↗
PubMed1987

Specific nuclear proteins interact with the Rous sarcoma virus internal enhancer and share a common element with the enhancer located in the long terminal repeat of the virus.

We have documented that the Rous sarcoma virus (RSV) internal enhancer functions in the nontransformed Baby Hamster Kidney (BHK) cell line. The sequences within this region were assayed for their ability to bind to specific factors present in BHK nuclear extracts using the gel retardation assay and DNAse I footprinting. At least two sequences within the internal enhancer which can specifically bind nuclear factors in vitro have been identified. These regions are located between nucleotides 813-850 and 856-877. These sites map within the overall region of the internal enhancer which has been shown to be essential for enhancer activity and within the specific region which can function as an orientation independent enhancer. Using the DNase I footprinting and binding data to design an oligonucleotide, we have demonstrated that an oligonucleotide extending from nucleotides 804-877 will substitute efficiently as an enhancer. We also demonstrate that the SV40 enhancer does not compete for the factors which bind to the RSV internal enhancer, whereas an oligonucleotide to the binding site for EFII in the LTR can compete for factor binding to the internal enhancer.

Animals↗
PubMed1991

Distinct cis-acting regions in U3 regulate trans-activation of the human spumaretrovirus long terminal repeat by the viral bel1 gene product.

The human spumaretrovirus (HSRV) genome contains, in addition to coding information for the structural proteins, open reading frames (ORFs) for at least three additional genes termed bel1, bel2 and bel3. We report here the localization of the transcriptional activator of HSRV to the bel1 ORF. In reporter-based transient expression assays in COS cells utilizing the bacterial CAT gene linked to HSRV LTR sequences between -710 and +309 with respect to the transcriptional initiation site, co-expression of the bel1 gene product alone caused an over 100 to 300-fold increase in the level of LTR activity. High-level trans-activation by bel1 was specific for the HSRV LTR, as relatively minor positive and negative regulatory effects were observed on HIV-1 LTR and RSV LTR expression, respectively, whereas HTLV-1 LTR activity remained unaffected. Distinct regions of the HSRV LTR were found to be involved in bel1-induced trans-activation. Specifically, deletions between -500 and -389 and between -136 and -62 in the U3 region resulted in a 4- and 30 to 35-fold decline, respectively, in the response to bel1. Limited mutagenesis of the bel1 ORF indicated that most of the bel1 coding region, except for the carboxy-terminal 27 residues, is essential for the activation function.

Amino Acid Sequence↗
PubMed2000

A developmentally regulated deletion element with long terminal repeats has cis-acting sequences in the flanking DNA.

Approximately 6000 specific DNA deletion events occur during development of the somatic macro-nucleus of the ciliate Tetrahymena. The eliminated Tlr1 element is 13 kb or more in length and has an 825 bp inverted repeat near the rearrangement junctions. A functional analysis of the cis -acting sequences required for Tlr1 rearrangement was performed. A construct consisting of the entire inverted repeat and several hundred base pairs of flanking DNA on each side was rearranged accurately in vivo and displayed junctional variability similar to the chromosomal Tlr1 rearrangement. Thus, 11 kb or more of internal element DNA is not required in cis for DNA rearrangement. A second construct with only 51 bp of Tetra-hymena DNA flanking the right junction underwent aberrant rearrangement. Thus, a signal for determination of the Tlr1 junction is located in the flanking DNA, 51 bp or more from the right junction. Within the Tlr1 inverted repeat are 19 bp tandem repeats. A construct with the 19mer repeat region deleted from the right half of the inverted repeat utilized normal rearrangement junctions. Thus, despite its transposon-like structure, Tlr1 is similar to other DNA rearrangements in Tetrahymena in possessing cis -acting sequences outside the deleted DNA.

Animals↗
PubMed1998

Protein-binding properties of the putative AP-1 and ATF sequences in the feline immunodeficiency virus long terminal repeat.

Electrophoresis-mobility-shift assays with nuclear extracts from a feline renal cell line and a T-lymphoblastoid cell line revealed that the AP-1 and ATF sites of feline immunodeficiency virus (FIV) TM2 strain had similar protein-binding properties to those of FIV Petaluma strain and consensus sequences of AP-1 and ATF sites, and that nuclear factors binding to these sites differed between the two cell lines. Cross-competition and gel-supershift assays demonstrated that the AP-1 and ATF sites had similar protein-binding properties. The effects of internal deletions of AP-1 and/or ATF sites on the basal promoter activity were also examined. Although deletion of either site moderately reduced activity, a mutant deleted in both sites had dramatically reduced activity. Therefore, we suggest that these two sites co-operatively regulate transcriptional activity of the promoter.

Activating Transcription Factors↗