Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analyzed protein-DNA interactions at the long terminal repeat of human immunodeficiency virus type 1 in a productively infected T-cell line by in vivo dimethyl sulfate footprinting. Major footprints are evident at the basal promoter and enhancer elements. In particular, proteins appear to occupy the TATA box, the Sp1 sites, and the two repeats of the enhancer region. In the negative regulatory element, protections are detected over the USF/MLTF and NFAT-1 sites. Furthermore, two previously unrecognized sites, from nucleotides -260 to -275 and from nucleotides -205 to -216, respectively, appear to be involved in protein-DNA interactions. These two sites are purine rich and share a common sequence motif.
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PMID:Probing protein-DNA interactions at the long terminal repeat of human immunodeficiency virus type 1 by in vivo footprinting. 154 76

Transcriptional regulation of the proviral form of the human immunodeficiency virus type 1 (HIV-1) is exerted by its 5' long terminal repeat (LTR), which contains recognition sites for several cell factors. By gel retardation and DNase I footprinting experiments we have identified a binding site for a human nuclear protein between nucleotides -152 to -174 upstream of transcription start site, in a region previously recognized as a negative regulator of transcription (negative regulatory element, NRE). The recognized sequence contains the dyad symmetry element CACGTG, which represents a binding motif, very conserved through evolution, present in a putative human DNA replication origin (pB48), in the upstream element of the major late promoter (MLP-UE) of adenovirus, and, as transcriptional element, upstream of many eukaryotic genes. Common binding activities exist in human nuclear extracts for pB48, MLP-UE and the HIV-1 LTR; at least three protein species recognize the LTR sequence, of 44 (corresponding to transcription factor USF/MLTF), 70, and 110 kDa, respectively. Chloramphenicol acetyltransferase assays suggest that the USF/MLTF binding site located in the HIV-1 LTR acts as a negative regulator of transcription, and that it contributes to the overall negative function exerted by the NRE. An oligonucleotide corresponding to another characterized human USF/MLTF binding site can functionally replace part of the activity of the NRE. This negative function is exerted both in presence or absence of tat transactivation, in different cell lines, and after PMA stimulation.
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PMID:A human binding site for transcription factor USF/MLTF mimics the negative regulatory element of human immunodeficiency virus type 1. 172 95

The TATA box-binding transcription factor TFIID from Saccharomyces cerevisiae was tested for its ability to mediate regulatory factor functions both in a cell-free system reconstituted with other general initiation factors (purified from HeLa cells) and in a combined nucleosome assembly-transcription system. In the latter assay recombinant yeast TFIID, expressed in and purified from bacteria, was sufficient to prevent nucleosome assembly-mediated repression and to mediate transcriptional enhancement of the adenovirus major late promoter by the gene-specific activator USF. In contrast, recombinant yeast TFIID was unable to mediate activation by USF in the system reconstituted only with purified general factors. Under the same conditions a partially purified natural yeast TFIID was able to mediate activation by both USF and Sp1 (assayed with the human immunodeficiency virus promoter), but to a lesser extent than observed with a partially purified natural human TFIID. The implications of these findings are discussed with respect to the structure of the yeast and human TATA factors and the possible involvement either of specific TFIID modifications or of coactivators.
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PMID:Recombinant yeast TFIID, a general transcription factor, mediates activation by the gene-specific factor USF in a chromatin assembly assay. 225 Dec 56

The negative regulatory element of human immunodeficiency virus type 1 is a 260-nucleotide-long sequence that decreases the rate of RNA transcription initiation specified by the long terminal repeat. This region has the potential to bind several cellular transcription factors. Here it is shown that sequences which recognize the NFAT-1 and USF cellular transcription factors contribute to this negative regulatory effect. The sequences within the negative regulatory element which resemble the AP-1 site and the URS do not negatively regulate human immunodeficiency virus long terminal repeat transcription initiation.
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PMID:Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1. 239 45

The human transcription factor USF, purified from HeLa cells, and its recombinant 43-kDa component bind to the long terminal repeat (LTR) of human immunodeficiency virus type 1. The proteins footprint over nucleotides from position -173 to -157 upstream of the transcription start site, generating strong DNAse I hypersensitivity sites at the 3' sides on both strands. As detected by methylation protection studies, the factor forms symmetric contacts with the guanines of the palindromic CACGTG core of the recognized sequence. Its binding ability is abolished by the mutation of this core sequence and is strongly reduced by the cytosine methylation of the central CpG dinucleotide. Upon binding, both recombinant and purified USFs bend the LTR DNA template. The role of USF in the control of transcription initiation from the LTR was tested by in vitro transcription assays. Upon addition of the protein, transcription from constructs containing an intact binding site is increased, while the responsiveness in constructs with a mutated sequence is abolished. Furthermore, the addition of a decoy plasmid which contains multiple repeats of the target sequence results in downregulation of transcription from the LTR. These results suggest that USF is a positive regulator of LTR-mediated transcriptional activation.
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PMID:Molecular and functional interactions of transcription factor USF with the long terminal repeat of human immunodeficiency virus type 1. 770 99

TFIID is a multisubunit protein complex comprised of the TATA-binding protein (TBP) and multiple TBP-associated factors (TAFs). The TAFs in TFIID are essential for activator-dependent transcription. The cloning of a complementary DNA encoding a human TFIID TAF, TAFII55, that has no known homolog in Drosophila TFIID is now described. TAFII55 is shown to interact with the largest subunit (TAFII230) of human TFIID through its central region and with multiple activators--including Sp1, YY1, USF, CTF, adenoviral E1A, and human immunodeficiency virus-type 1 Tat proteins--through a distinct amino-terminal domain. The TAFII55-interacting region of Sp1 was localized to its DNA-binding domain, which is distinct from the glutamine-rich activation domains previously shown to interact with Drosophila TAFII110. Thus, this human TFIID TAF may be a co-activator that mediates a response to multiple activators through a distinct mechanism.
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PMID:Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. 782 54

Current understanding of human immunodeficiency virus type 1 (HIV-1) transcription is based on unidirectional expression of transcripts with positive-strand polarity from the 5' long terminal repeat. We now report HIV-1 transcripts with negative-strand polarity obtained from acutely and chronically infected cell lines by use of a template orientation-specific reverse transcriptase-PCR assay. These findings were confirmed in natural infection by analysis of RNA derived from peripheral blood mononuclear cell samples from 15 HIV-1-infected patients. A cDNA derived from a 2.3-kb polyadenylated HIV-1 RNA with negative-strand polarity which encodes a highly conserved 189-amino-acid open reading frame antiparallel to the envelope gene was isolated from acutely infected A3.01 cells. Through use of reporter gene constructions, we further found that a novel negative-strand promoter functions within the negative response element of the 3' long terminal repeat, which is downregulated by coexpression of Tat. Site-directed mutagenesis experiments demonstrated that NF-kappa B I and USF sites are crucial for negative-strand promoter activity. These data extend the coding capacity of HIV-1 and suggest a role for antisense regulation of the viral life cycle.
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PMID:Negative-strand RNA transcripts are produced in human immunodeficiency virus type 1-infected cells and patients by a novel promoter downregulated by Tat. 828 99

We previously demonstrated that hepatitis C virus (HCV) core protein is a strong repressor of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) basal transcription. In this study, we have localized the HCV core protein-response domain to a region between nucleotides -65 and +3 within the HIV-LTR. Thus, neither the upstream negative regulatory elements, or binding sites for various transcription factors (e.g. NF-kappa B, USF-1, IL2/IL-2R) nor the downstream TAR regions were involved in HCV core-mediated repression. HCV core protein mediated repression of the basal transcriptional activity of HIV-1 LTR was abrogated by the Tat protein. Furthermore, HeLa-T4 cells expressing HCV core protein showed inhibition of HIV-1 replication after acute infection with cell-free HIV. A similar observation was also noted in CD4+ and CD4-lymphocytic cell lines cotransfected with an infectious molecular clone of HIV-1 and the HCV core protein expression vector. Thus, a repression of basal transcription prior to the accumulation of threshold levels of Tat protein appears to restrict HIV-1 transcription and modulate viral replication.
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PMID:Hepatitis C virus core protein inhibits human immunodeficiency virus type 1 replication. 889 43

To investigate mechanisms yielding DNase I-hypersensitive sites (DHSs) at gene regulatory regions, we have initiated a biochemical analysis of transcription factor binding and nucleosome remodeling with a region of the human immunodeficiency virus 1 (HIV-1) 5' long terminal repeat (LTR) that harbors constitutive DHSs in vivo. In vitro reconstitution of an HIV-1 5' LTR fragment into nucleosome core particles demonstrates that Sp1, NF-kappaB1, LEF-1, ETS-1 and USF can gain access to their binding sites in HIV-1 nucleosomal DNA. The factor-bound mononucleosomes resist histone displacement from the DNA by the chromatin remodeling activity, SW1-SNF, or the histone chaperone, nucleoplasmin, suggesting that the binding of these factors to nucleosomal HIV-1 sequences forms a stable complex that includes the underlying histones. However, when the HIV-1 5' LTR fragment is incorporated into a nucleosomal array, Sp1 and NF-kappaB1 binding produce regions of enhanced DNase I sensitivity specifically at the HIV-1 nucleosome. These regions resemble the observed in vivo DHSs, yet the HIV-1 nucleosome remains intact even in the presence of nucleoplasmin. Thus, the constitutive DHSs identified at the HIV-1 enhancer in native chromatin may reflect the presence of a ternary complex composed of transcriptional activators, histones and DNA.
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PMID:Stable co-occupancy of transcription factors and histones at the HIV-1 enhancer. 917 59

The distal enhancer region of the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR) is known to be essential for HIV replication and to contain immediately adjacent E-box and Ets binding sites. Based on a yeast one-hybrid screen we have identified the E-box binding protein USF-1 as a direct interaction partner of Ets-1 and found that the complex acts on this enhancer element. The binding surfaces of USF-1 and Ets-1 map to their DNA-binding domains and although these domains are highly conserved, the interaction is very selective within the respective protein family. USF-1 and Ets-1 synergize in specific DNA binding as well as in the transactivation of reporter constructs containing the enhancer element, and mutations of the individual binding sites dramatically reduce reporter activity in T cells. In addition, a dominant negative Ets-1 mutant inhibits both USF-1-mediated transactivation and the activity of the HIV-1 LTR in T cells. The inhibition is independent of Ets DNA-binding sites but requires the Ets binding surface on USF-1, highlighting the importance of the direct protein-protein interaction. Together these results indicate that the interaction between Ets-1 and USF-1 is required for full transcriptional activity of the HIV-1 LTR in T cells.
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PMID:Cooperative interaction of ets-1 with USF-1 required for HIV-1 enhancer activity in T cells. 950 Oct 94


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