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PubMed2000

Insertion of a retroviral solo long terminal repeat in mdr-3 locus disrupts mRNA splicing in mice.

Previously, the abermectin-induced neurotoxicity of subpopulation of CF-1 mice was shown to be caused by the deficiency of mdr-3 P-glycoprotein. Here, we have characterized the molecular nature of the mdr-3 gene mutation in this subpopulation of CF-1 mice. The size of mdr-3 mRNA transcript from ivermectin-sensitive mutant mice was different from that of wild-type mice. Sequence analysis of RT-PCR products isolated from the mutant brain disclosed that the exon 23 of the mdr-3 gene is deleted or altered in the transcripts. The analysis of the genomic locus revealed an insertion of a solo long terminal repeat (LTR) of the ecotropic murine leukemia virus in the reverse orientation in the intron of the mdr-3 gene, causing abnormal splicing and thereby disrupting the mdr-3 gene function. In addition, histopathological analysis of the brains of the ivermectin-treated mutants revealed selective neuronal degeneration in the hippocampal CA3 region. This is the first reported case of a gene mutation induced by a solo retroviral LTR with a phenotypic consequence in the mouse, and may provide new insights into the understanding of the effects of viral solo LTR sequences on mammalian gene expression.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1992

Mls-1 is encoded by the long terminal repeat open reading frame of the mouse mammary tumor provirus Mtv-7.

The murine Mls-1 antigen is the prototype of endogenous superantigens, molecules whose activities lead to deletion of T cells expressing certain T-cell receptor V beta genes from the mature repertoire. However, Mls-1 also stimulates T cells expressing these particular V beta genes (V beta 6, V beta 7, V beta 8.1, and V beta 9) in vitro, making it one of the strongest known T-cell activators. We have recently reported that the Mls-1 gene is closely linked to the endogenous mammary tumor virus Mtv-7. We now demonstrate that Mls-1 is encoded by the open reading frame in the U3 region of the long terminal repeat of Mtv-7. However, control of expression of this molecule seems complex, depending on the promoter used for the transfection experiments. The sequence of the Mtv-7 open reading frame differs from all other known mammary tumor virus open reading frame sequences in the 3' end, suggesting that the T-cell receptor V beta specificity is conferred by the C terminus of the molecule. The predicted structure of the protein encoded by the open reading frame is consistent with a type II transmembrane molecule where the C terminus is extracellular.

Amino Acid Sequence↗
PubMed2000

A murine leukemia virus (MuLV) long terminal repeat derived from rhesus macaques in the context of a lentivirus vector and MuLV gag sequence results in high-level gene expression in human T lymphocytes.

We constructed human immunodeficiency virus type 1 (HIV-1) vectors that will allow higher levels of gene expression in T cells. Gene expression under the control of an internal cytomegalovirus (CMV) immediate-early promoter in a self-inactivating lentiviral vector (CSCG) is 4- to 15-fold lower in T-cell lines (SUPT1 and CEMX174) than in non-lymphoid-cell lines (HeLa and 293T). This is in contrast to a Moloney murine leukemia virus (MoMLV)-based retrovirus vector (SRalphaLEGFP). We therefore replaced the internal CMV promoter of CSCG with three different murine oncoretroviral long terminal repeat (LTR) promoters-murine sarcoma virus (MSV), MoMLV (MLV), and the LTR (termed Rh-MLV) that is derived from the ampho-mink cell focus-forming (AMP/MCF) retrovirus in the serum of one rhesus macaque monkey that developed T-cell lymphoma following autologous transplantation of enriched bone marrow stem cells transduced with a retrovirus vector preparation containing replication-competent viruses (E. F. Vanin, M. Kaloss, C. Broscius, and A. W. Nienhuis, J. Virol. 68:4241-4250, 1994). We found that the combination of Rh-MLV LTR and a partial gag sequence of MoMLV (Deltagag(871-1612)) in CS-Rh-MLV-E gave the highest level of enhanced green fluorescent protein (EGFP) gene expression compared with MLV, MSV LTR, phosphoglycerate kinase, and CMV promoters in T-cell lines, as well as activated primary T cells. Interestingly, there was a further two- to threefold increase in EGFP expression (thus, 10-fold-higher expression than with CMV) when the Rh-MLV promoter and Deltagag(871-1612) were used in a self-inactivating-vector setting that has a further deletion in the U3 region of the HIV-1 LTR. These hybrid vectors should prove useful in gene therapy applications for T cells.

Animals↗
PubMed1982

Leukemogenesis by bovine leukemia virus: proviral DNA integration and lack of RNA expression of viral long terminal repeat and 3' proximate cellular sequences.

The DNA from 17 lymphoid tumors induced by bovine leukemia virus (BLV) was digested with the restriction endonuclease EcoRI. Filter hybridization analysis using radioactive probes specific for the BLV genome showed that all tumors contained at least one or a portion of one provirus. Digestion of these proviruses with Sac I demonstrated that deletions occurred in about 25% of the cases and involved sequences located in the 5' half of the provirus. No sequence homology was observed between the cloned proximate cellular sequences flanking two different proviruses at their 3' end and the corresponding sequences in 16 other tumor DNAs, thus showing that a wide range of genomic sites could accommodate BLV proviruses. Transcription of viral DNA including long terminal repeated sequences was not detected, strongly suggesting that viral gene expression is not required for maintenance of the tumor state. No expression of 3'-proximate cellular sequences was observed, indicating that no proximate downstream promotion took place in the cases examined.

Animals↗
PubMed1997

The U3 region of the long terminal repeat of a subgroup A transformation-defective rous sarcoma virus (tdPH2010) converts a noncytopathic virus to a cytopathic virus.

The molecular basis of the cytopathic effects (CPE) of the transformation-defective avian retrovirus mutant, tdPH2010, was studied. tdPH2010 is a subgroup A virus isolated from the Schmidt-Ruppin (NY) subgroup A strain (SRA(NY)). Subgroup A avian retroviruses are generally considered noncytopathic. Integrated tdPH2010 was molecularly cloned from infected quail cells. A noncytopathic, transformation-defective control strain, BSU, was created by deleting the src gene from the molecularly cloned wild type SRA(NY) virus. Chimeras between tdPH2010 and BSU were constructed and viruses were recovered from transfected chick embryo fibroblasts. Growth curves of cells infected with chimeric viruses indicated that the long terminal repeat (LTR) of tdPH2010 converts BSU to a cytopathic virus. Nucleotide sequencing revealed two point mutations unique to tdPH2010 in the U3 region of LTR at positions -126 and -23 from the transcription start site. Both mutations were located inside or near the promoter/enhancer elements of U3. The mutation at -126 (G to T) converted one of the very well-conserved pentanucleotide repeat (PRE) motifs from GGTGG to GGTGT. The other at -23 (G to A) is located next to the TATA box. The G at this position is conserved in all other known avian retrovirus promoters.

Animals↗
PubMed1998

Identification and analysis of Mot3, a zinc finger protein that binds to the retrotransposon Ty long terminal repeat (delta) in Saccharomyces cerevisiae.

Spt3 and Mot1 are two transcription factors of Saccharomyces cerevisiae that are thought to act in a related fashion to control the function of TATA-binding protein (TBP). Current models suggest that while Spt3 and Mot1 do not directly interact, they do function in a related fashion to stabilize the TBP-TATA interaction at particular promoters. Consistent with this model, certain combinations of spt3 and mot1 mutations are inviable. To identify additional proteins related to Spt3 and Mot1 functions, we screened for high-copy-number suppressors of the mot1 spt3 inviability. This screen identified a previously unstudied gene, MOT3, that encodes a zinc finger protein. We show that Mot3 binds in vitro to three sites within the retrotransposon Ty long terminal repeat (delta) sequence. One of these sites is immediately 5' of the delta TATA region. Although a mot3 null mutation causes no strong phenotypes, it does cause some mild phenotypes, including a very modest increase in Ty mRNA levels, partial suppression of transcriptional defects caused by a mot1 mutation, and partial suppression of an spt3 mutation. These results, in conjunction with those of an independent study of Mot3 (A. Grishin, M. Rothenberg, M. A. Downs, and K. J. Blumer, Genetics, in press), suggest that this protein plays a varied role in gene expression that may be largely redundant with other factors.

Adenosine Triphosphatases↗
PubMed1999

HIV-1 Nef alters the expression of betaII and epsilon isoforms of protein kinase C and the activation of the long terminal repeat promoter in human astrocytoma cells.

In the human immunodeficiency virus type 1 (HIV-1)-infected brain, the virus does not replicate in astrocytes, but a synthesis of viral regulatory proteins occurs in these cells, leading to accumulation of Nef. As an approach to understand the effects of Nef on astrocyte functional activity, we analyzed whether intracellular Nef interferes with the expression and activation of the enzyme protein kinase C (PKC), which is an important regulator of astroglial functions and HIV-1 replication. Astrocytoma clones (U251 MG) not expressing Nef (Neo), or expressing wild-type Nef (Bru) or nonmyristoylated Nef (TH) were used to monitor the expression and activation of 10 PKC isoforms. The same clones were used to evaluate the effect of Nef on the viral long terminal repeat (LTR) promoter after activation of PKC with the phorbol ester 12-myristate 13-acetate (PMA). PKC intracellular distribution and activation were evaluated by Western blot analysis of cytosolic and membrane fractions of control and Nef-expressing clones. PMA-induced LTR activation was analyzed in clones transfected with a plasmid encoding for the CAT reporter gene controlled by the LTR promoter, by using an enzyme-linked immunosorbent assay to measure CAT expression. Nef selectively downregulated the expression and activation of betaII and epsilon PKC isoforms in astrocytoma cells. Such downregulation correlated with an inhibition of LTR activation after PMA stimulation. The myristoylation of Nef and its membrane localization were essential for these effects. These results suggest that Nef may alter astrocytic functions by interfering with PKC expression and activation and contribute to the restriction of HIV-1 replication in astrocytes.

AIDS Dementia Complex↗
PubMed1993

Pao, a highly divergent retrotransposable element from Bombyx mori containing long terminal repeats with tandem copies of the putative R region.

Analysis of aberrant ribosomal DNA (rDNA) repeats of Bombyx mori resulted in the discovery of a 4.8 kilobase retrotransposable element, Pao. Approximately 40 copies of Pao are present in the genome with most located outside the rDNA units. The complete sequence of one Pao element and partial sequence of four other copies indicated that Pao encodes an 1158 amino acid open-reading frame (ORF). Located within this ORF are domains with sequence similarity to retroviral gag genes, aspartic protease and reverse transcriptase. RNase H and integrase domains were not identified suggesting that the cloned copies were not full-length elements. Pao elements contain long terminal repeats (LTRs) with a central region composed of variable numbers of 46 bp tandem repeats. The variable region appears to correspond to the R region of retroviral LTRs, the region responsible for strand transfer during reverse transcription. Based on a sequence analysis of its reverse transcriptase domain, Pao is most similar to TAS of Ascaris lumbricoides. Pao and TAS represent a subgroup of LTR retrotransposons distinct from the Copia-Ty1 and Gypsy-Ty3 subgroups.

Amino Acid Sequence↗
PubMed1996

Retroviral insertional activation in a herpesvirus: transcriptional activation of US genes by an integrated long terminal repeat in a Marek's disease virus clone.

Insertional activation of host proto-oncogenes has been recognized as a basic mechanism by which nonacute retroviruses induce cancer. Our previous work has demonstrated that retroviruses can efficiently integrate into DNA virus genomes. Specifically, coinfection of cultured fibroblasts with a chicken herpesvirus, Marek's disease virus (MDV), and a chicken retrovirus results in frequent stable retroviral insertions into the herpesvirus genome. Such insertions could alter the expression of herpesvirus genes, possibly resulting in novel phenotypic properties. In this article, we report the characterization of a replication-competent clone of MDV with integrated retroviral sequences. This virus was isolated from a chicken following injection of fibroblasts coinfected with MDV and the retrovirus, reticuloendotheliosis virus. Transcripts originating from the reticuloendotheliosis virus long terminal repeat promoters were found to encode the adjoining MDV genes, SORF2, US1, and US10. This virus replicates well in culture but has an unusual phenotype in chickens, characterized by an attenuated virulence which produces no nerve lesions but, rather, severe thymic atrophy. While the causal relationship between the insertion and the observed phenotypes remains to be established, our data provide the first evidence of retroviral insertional activation of herpesvirus genes.

Amino Acid Sequence↗
PubMed1997

Complete nucleotide sequence of the new simian T-lymphotropic virus, STLV-PH969 from a Hamadryas baboon, and unusual features of its long terminal repeat.

A third type of primate T-lymphotropic virus, PTLV-L, with STLV-PH969 as a prototype, has recently been isolated from an African baboon (Papio hamadryas). Classification of this virus has been based on partial sequence analysis of cDNA from a virus-producing cell line, PH969. We obtained the complete nucleotide sequence of this virus with a proviral genome of 8,916 bp. All major genes, homologous in all human T-cell lymphotropic virus (HTLV)-related viruses, and their corresponding mRNAs, including appropriate splicing, were identified. One additional nonhomologous open reading frame in the proximal pX region is accessible for translation through alternative splicing. Sequence comparison shows that STLV-PH969 is equidistantly related to HTLV type 1 (HTLV-1) and HTLV-2. In all coding regions, the similarity tends to be the lowest between STLV-PH969 and HTLV-1. However, in the long terminal repeat (LTR) region, the lowest similarity was found between STLV-PH969 and HTLV-2. The U3-R and R-U5 boundaries of the STLV-PH969 LTR were experimentally determined at nucleotides 268 and 524, respectively. This 695-bp LTR is 60 and 73 bp shorter than the LTRs of HTLV-1 and HTLV-2, respectively, but its general organization is similar to the one found in the HTLV-bovine leukemia virus genus. In the long region between the polyadenylation signal and the poly(A) site, sequence similarity with the HTLV-1 Rex-responsive element (RexRE) core and secondary structure prediction suggest the presence of a RexRE. The presence of three 21-bp repeats is conserved within the U3 region of HTLV-1, HTLV-2, and BLV. Only two direct repeats with similarity to these Tax-responsive elements were found in the STLV-PH969 LTR, which might suggest differences in the Tax-mediated transactivation of this virus. We conclude that STLV-PH969 has all the genes and genomic regions to suggest a replication cycle comparable to that of HTLV-1 and HTLV-2.

Amino Acid Sequence↗
PubMed1989

Retroviral long terminal repeat is the promoter of the gene encoding the tumor-associated calcium-binding protein oncomodulin in the rat.

Oncomodulin is a small calcium-binding protein normally found only in extra-embryonic tissues such as the placenta, but whose presence in a variety of tumors has been documented. We have isolated the oncomodulin gene from a Buffalo rat genomic library. The rat gene is approximately 9000 bases in length and consists of five exons and four introns. The introns interrupt the coding sequence of oncomodulin in positions identical with those previously reported for the parvalbumin gene, indicating that the two genes are derived from a common ancestor. Analysis of the promoter sequence of the oncomodulin gene revealed that the gene is under the control of a solo long terminal repeat element related to intracisternal-A particles, a family of endogenous retroviral elements. This represents a unique example of a mammalian gene transcribed in normal and tumor cells, from a promoter of viral origin.

Amino Acid Sequence↗
PubMed1988

Alterations in the U3 region of the long terminal repeat of an infectious thymotropic type B retrovirus.

We isolated and characterized a type B thymotropic retrovirus (DMBA-LV) which is highly related to mouse mammary tumor virus (MMTV) isolates and which induces T-cell thymomas with a high incidence and a very short latent period. Regions of nonhomology between the DMBA-LV genome and the MMTV genome were identified by heteroduplex mapping and nucleotide sequence studies. In the electron microscope heteroduplex mapping studies the EcoRI-generated 5' and 3' fragments of the DMBA-LV genome were compared with the corresponding fragments of the MMTV (C3H and GR) genome isolated from mammary tumors. The results indicated that DMBA-LV contained a region of nonhomologous nucleotide sequences in the 3' half of the U3 region of the long terminal repeat (LTR). Nucleotide sequence studies confirmed these results and showed that in this region 440 nucleotides of the MMTV (C3H) sequences were deleted and substituted with a segment of 122 nucleotides. This substituted segment in the form of a tandem repeat structure contained nucleotide sequences derived exclusively from sequences which flanked the substitution loop. The distal glucocorticoid regulatory element was unaltered, and two additional copies of the distal glucocorticoid regulatory element-binding site were present in the substituted region. The restriction endonuclease map of the reconstructed molecular clone of DMBA-LV was identical to that corresponding to unintegrated linear DMBA-LV DNA present in DMBA-LV-induced tumor cell lines. Since the nucleotide sequences of the LTRs present in four different DMBA-LV proviral copies isolated from a single thymoma were identical, we concluded that they were derived from the same parental virus and that this type B retrovirus containing an alteration in the U3 region of its LTR could induce thymic lymphomas. Thus, DMBA-LV represents the first example of a productively replicating type B retrovirus that contains an LTR modified in the U3 region and that has target cell and disease specificity for T cells.

Base Sequence↗
PubMed1985

A viral long terminal repeat in the interleukin 2 gene of a cell line that constitutively produces interleukin 2.

The gibbon leukemia cell line MLA 144 differs from every other T-lymphocyte line in that it constitutively makes interleukin 2 (IL-2) (also called T-cell growth factor) without stimulation by antigen, lectin, or tumor promoters. Previous work in which glucocorticoids were used to inhibit IL-2 production has indicated that proliferation of this cell line is dependent upon endogenously produced IL-2. We have found that the MLA 144 cell line has a copy of the gibbon leukemia virus inserted into the 3' nontranslated region of the IL-2 gene. This integration event produces a composite mRNA made up of the protein coding sequences of the IL-2 gene transcript but incorporating the viral long terminal repeat (LTR) in the 3' nontranslated region of the mRNA. This composite mRNA transcript uses the polyadenylylation signal in the viral 5' LTR and incorporates the viral transcriptional control regions. The integration event must involve only one allele of the IL-2 gene, since transcripts essentially identical to normal human IL-2 mRNA are also produced in cloned sublines of MLA 144. That the viral LTR contains a 94-base-pair repeat reminiscent of enhancer sequences in several viruses suggests that the integration of the viral LTR at the 3' end of the IL-2 gene is responsible for the constitutive production of IL-2 in the MLA 144 cell line.

Animals↗
PubMed1999

Screening by tRNA primer extension analysis of porcine kidney mRNA libraries defines a novel endogenous porcine retroviral long terminal repeat.

BACKGROUND: We have taken advantage of the common requirement of all eukaryotic retroelements for a specific tRNA primer to initiate DNA synthesis and applied a previously described in vitro screening methodology to the analysis of in vivo porcine tissues for transcriptionally active retroviral sequences. METHODS: A series of 18-base pair (bp) 3' tRNA oligomers complementary to established primer binding sites for a variety of vertebrate retroviruses, retrotransposons, and retroposons were applied to primer extension analysis of kidney poly(A) mRNA. Primer extension products are predicted to represent "strong stop" signals characteristic of the initial stages of retroviral transcription. RESULTS: Several extension products were cloned, sequenced, and analyzed as probes for screening the porcine genome for potentially active retroviral sequences. We used this strategy to identify and clone a 655-bp 5' long terminal repeat of a porcine retrovirus with significant homology to the simian sarcoma virus. This transcriptionally active virus has an 82-bp U5 region, a conserved AATAAA polyadenylation sequence, a 39-bp repeat reminiscent of other retroviral enhancers, and a unique glycine primer binding site. CONCLUSION: Our results suggest that tRNA primer cloning can effectively identify novel retroviral elements.

Animals↗
PubMed1999

Evidence for the recent horizontal transfer of long terminal repeat retrotransposon.

The evolutionary dynamics existing between transposable elements (TEs) and their host genomes have been likened to an "arms race." The selfish drive of TEs to replicate, in turn, elicits the evolution of host-mediated regulatory mechanisms aimed at repressing transpositional activity. It has been postulated that horizontal (cross-species) transfer may be one effective strategy by which TEs and other selfish genes can escape host-mediated silencing mechanisms over evolutionary time; however, to date, the most definitive evidence that TEs horizontally transfer between species has been limited to class II or DNA-type elements. Evidence that the more numerous and widely distributed retroelements may also be horizontally transferred between species has been more ambiguous. In this paper, we report definitive evidence for a recent horizontal transfer of the copia long terminal repeat retrotransposon between Drosophila melanogaster and Drosophila willistoni.

Animals↗
PubMed1996

Concerted integration of linear retroviral DNA by the avian sarcoma virus integrase in vitro: dependence on both long terminal repeat termini.

We have reconstituted integration reactions in vitro with specially designed donor DNAs, a supercoiled plasmid acceptor, purified bacterium-derived Rous sarcoma virus integrase (IN), and a host cell DNA-bending protein, HMG1. The duplex donor DNAs are approximately 300 deoxynucleotides in length and contain only 15 bp of the RSV U3 and U5 termini at the respective ends. The donor has blunt U3 and U5 termini which end with the sequence 5'CATT. Joining of the donor DNA to the acceptor DNA is detected by using a simple biochemical assay. Integration was found to be dependent on both U3 and U5 termini; mutations in either result in a significant decrease in the level of integration in vitro. Restriction digestion of the products is consistent with most integrants representing a concerted integration in which both long terminal repeat termini come from the same donor molecule. The U5 and U3 sequences in the substrate flank a supF tRNA gene, permitting biological selection of integrants. Many integrants have been sequenced, and have all of the hallmarks of authentic viral integration, including the removal of a terminal TT dinucleotide from each donor DNA end, and duplication of acceptor sequences at the integration site without introducing deletions into the acceptor. Target site selection in the acceptor plasmid was random except that the orientation of integrants selected was apparently influenced by supF transcription. Mutations which substituted the conserved CA dinucleotide with a GA pair led to a decreased rate of integration. In 2 of 14 mutant integrants sequenced, deoxynucleotides were deleted from either the U5 or U3 terminus. In one instance, an internal CA dinucleotide was used, which resulted in a 10-bp U5 donor deletion. In the other, an internal GA dinucleotide was used, which produced a 5-bp U3 donor deletion. Both of these integrants provide further evidence that concerted integration in this reconstituted system requires interactions between IN and the U3 and U5 termini from the same donor molecule.

Avian Sarcoma Viruses↗
PubMed1997

Mapping of a major osteomagenic determinant of murine leukemia virus RFB-14 to non-long terminal repeat sequences.

Certain isolates of murine leukemia viruses (MuLVs) have, apart from a leukemogenic potential, the capability of inducing diseases of nonhematopoietic tissues in susceptible strains of mice. We have reported on the molecular cloning of a bone-tumorigenic virus, RFB-14 MuLV, which was found to induce benign bone tumors, osteomas, with 100% incidence in mice of the CBA/Ca strain (L. Pedersen, W. Behnisch, J. Schmidt, A. Luz, F. S. Pedersen, V. Erfle, and P. G. Strauss, J. Virol. 66:6186-6190, 1992). In order to analyze the bone tumor-inducing phenotype of RFB-14 MuLV, we have studied the pathogenic potential of recombinant viruses between RFB-14 and the nonosteomagenic, highly leukemogenic SL3-3 MuLV. The recombinants were constructed so as to reveal whether a major determinant of osteomagenicity maps to sequences within or outside the long terminal repeats (LTR). Our data show that a major determinant of the osteoma-inducing potential of RFB-14 MuLV maps to the non-LTR region of the genome. Furthermore, we demonstrate that a strong determinant of leukemogenicity is harbored by the non-LTR region of SL3-3 MuLV.

3T3 Cells↗
PubMed1984

Covalent and noncovalent receptor-glucocorticoid complexes preferentially bind to the same regions of the long terminal repeat of murine mammary tumor virus proviral DNA.

Dexamethasone 21-mesylate, an irreversible antiglucocorticoid in HTC cells, forms a covalent receptor-steroid complex which can be activated in cell-free systems. The molecular basis of its antiglucocorticoid activity is unknown; it might result from altered DNA sequence preferences and/or affinities of the covalent receptor-steroid complex. To test this hypothesis, the affinities of both covalent receptor-antagonist and noncovalent receptor-agonist complexes for defined DNA sequences were measured in a DNA binding competition assay. This assay requires neither purified complexes nor large quantities of DNA, yet it provides quantitative comparisons of the affinities of different double-stranded DNAs for binding receptor-steroid complexes. In this assay, activated covalent receptor-dexamethasone 21-mesylate complexes in crude cytosol bound to calf thymus DNA and cloned subregions of the long terminal repeat (LTR) of murine mammary tumor virus (MMTV) proviral DNA with approximately the same relative affinities as did noncovalent receptor-dexamethasone complexes. Both types of complex exhibited similar orders of preferential binding to DNA sequences. LTR subregions, as well as the entire LTR, were 2-20 times more potent competitors than calf thymus DNA. Cloned sequences from the 3' terminus of the LTR were more effective competitors than either the entire LTR or comparably sized DNAs from the 5' terminus. The DNA sequences with the greatest affinities for both covalent and noncovalent complexes are located within the region of -221 to -67. These studies support the theory that recognition by regulatory elements of specific DNA sequences upstream of responsive genes is an integral step of hormone action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗