A novel cis-acting element that controls transcription of human immunodeficiency virus type 1 DNA, depending on cell type

Nakanishi, Yoshinobu; Masamune, Yukito; Kimura, Noriaki

doi:10.1128/jvi.65.11.6334-6338.1991

Cited by 14 publications

(13 citation statements)

References 52 publications

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“…Sequences in the promoter (Spl binding sites and the TATA motif) and enhancer (NF-KB binding sequence) regions constituted the most influential positive control elements for basal LTR activity in both stimulated and unstimulated macrophages. The importance of NF-KB, Spl, and TATA elements in mediating transcriptional activation of the HIV LTR has been shown in T-cell systems (15,18,20,22,26,28,29,36,38,41) and in a monocytic cell line (28). Importantly, the present study identifies these sequences as a vital transcriptional control in primary macrophages.…”

Section: Discussionsupporting

confidence: 53%

“…The activation state of the HIV LTR may also be influenced by negative control elements. Studies in a number of different cellular systems report the negative influence of the NRE on LTR activity (8,22,24,25,28,41). In the primary macrophage system, use of an LTR construct containing upstream NRE sequences caused an up to fivefold decrease in LTR activity relative to that of the wild type in both stimulated and unstimulated macrophages (data not shown).…”

Section: Differential Role Of Ltr Control Elementsmentioning

confidence: 94%

“…To date, the majority of studies addressing transcriptional regulation of the HIV LTR have been performed with HeLa cells (2,7,8,13,15,20,40) and T-cell lines (13, 15, 22-26, 28, 30, 31, 33, 40, 41). Additional studies have included a B-cell line (40), a megakaryocyte cell line (33), and the monocytic cell line U937 (15, 24,28). Studies with primary human cells have been limited to those employing peripheral blood T cells (30,32).…”

mentioning

confidence: 99%

“…Results from these studies have identified sequence elements on the LTR that are important in regulating the level of viral transcription in either a positive or a negative fashion. Sequences that enhance transcription include, in the U3 region, a tandemly repeated enhancer ( -103 to -81) recognized by NF-KB (27) and EBP-1 (40), three Spl binding sites (-75 to -47 [8,19]), the TATA box (-28 to -24) recognized by TFIID and other TATA-binding factors (8), an upregulatory element (URE; -157 to -122 [28]) and in the untranslated leader (R) region, direct repeat sequences recognized by the cellular protein UBP-1 (8) (or LBP-1 [20]), UBP-2 (7), or CTF/NF 1 (20) and the trans activation response (TAR) element (+ 14 to +44), which is responsive to the viral trans-activator protein Tat (31). Sequences with the potential to decrease the synthesis of viral RNA include the negative regulatory element (-419 to -157) recognized by cellular DIFFERENTIAL ROLE OF LTR CONTROL ELEMENTS 299 factors including AP-1, NFAT-1, URS, and USF (6,8,35) and sequence elements flanking the TATA region which bind UBP-1 (LBP-1) (21).…”

mentioning

confidence: 99%

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Differential role of long terminal repeat control elements for the regulation of basal and Tat-mediated transcription of the human immunodeficiency virus in stimulated and unstimulated primary human macrophages

Moses

Ibañez

Gaynor

et al. 1994

J Virol

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Primary human macrophages induced to differentiate through contact with autologous activated nonadherent cells were used to investigate the transcriptional mechanisms involved in reactivation of human immunodeficiency virus (HIV) replication. Through transient transfection experiments with an HIV long terminal repeat (LTR)-chloramphenicol acetyltransferase reporter construct, we show that macrophage differentiation results in a 20-fold upregulation of basal LTR activity. To identify sequence elements responsive to the differentiation process, point mutations introduced into the LTR were tested in differentiated and undifferentiated macrophages. Several elements were identified as positive regulators of basal transcription. TATA, Spl, and NF-KB binding sites were the most influential. The low-affinity site for LBP-1 (UBP-1) functioned as a negative regulator of LTR activity in undifferentiated macrophages, but this influence was lost upon differentiation. When tat was cotransfected into the expression system, the requirement for LTR elements identified as important for positive regulation of basal transcription remained in undifferentiated macrophages. Interestingly, however, the mutations in positive control elements which debilitated activity in undifferentiated macrophages had no effect on LTR activity in differentiated macrophages. Thus, it appears that while HIV-LTR activity is highly dependent on cellular transcription factors in undifferentiated cells, in differentiated macrophages the viral protein Tat confers pliability on the LTR and facilitates autonomy from absolute cellular control mechanisms. In vivo, release from either positive or negative regulation via cellular proteins may facilitate reactivation of HIV in macrophages.

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Section: Discussionsupporting

confidence: 53%

Section: Differential Role Of Ltr Control Elementsmentioning

confidence: 94%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Differential role of long terminal repeat control elements for the regulation of basal and Tat-mediated transcription of the human immunodeficiency virus in stimulated and unstimulated primary human macrophages

Moses

Ibañez

Gaynor

et al. 1994

J Virol

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“…1). The LTR/Nef-coding region of the prototypical HIV-1 LTR consists of a negative regulatory region (Ϫ340 to Ϫ185) (7,57) and an upstream regulatory element (URE) (Ϫ157 to Ϫ122) (54). The negative regulatory region contains binding sites for the nuclear factor of activated T cells (NF-AT) (47,61) and upstream stimulatory factor (17), while the URE includes binding sites for lymphoid enhancer-binding factor (hLEF; also referred to as TCF-1␣) (62,66,70), Ets-1 (34,62), and Ras-responsive binding factors 1 and 2 (RBF-1 and -2), which bind to Ras-responsive binding elements (RBE) IV (Ϫ151 to Ϫ142) and RBE III (Ϫ131 to Ϫ122) (6,22) (Fig.…”

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confidence: 99%

Naturally Occurring Human Immunodeficiency Virus Type 1 Long Terminal Repeats Have a Frequently Observed Duplication That Binds RBF-2 and Represses Transcription

Estable

Bell²,

Hirst³

et al. 1998

J Virol

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Approximately 38% of human immunodeficiency virus type 1 (HIV-1)-infected patients within the Vancouver Lymphadenopathy-AIDS Study have proviruses bearing partial 15- to 34-nucleotide duplications upstream of the NF-κB binding sites within the 5′ long terminal repeat (LTR). This most frequent naturally occurring length polymorphism (MFNLP) of the HIV-1 5′ LTR encompasses potential binding sites for several candidate transcription factors, including TCF-1α/hLEF, c-Ets, AP-4, and Ras-responsive binding factor 2 (RBF-2) (M. C. Estable et al., J. Virol. 70:4053–4062, 1996). RBF-2 and an apparently related factor, RBF-1, bind to at least fourcis elements within the LTR which are required for full transcriptional responsiveness to protein-tyrosine kinases and v-Ras (B. Bell and I. Sadowski, Oncogene 13:2687–2697, 1996). Here we demonstrate that representative MFNLPs from two patients specifically bind RBF-2. In both cases, deletion of the MFNLP caused elevated LTR-directed transcription in cells expressing RBF-2 but not in cells with undetectable RBF-2. RBF-1, but not RBF-2, appears to contain the Ets transcription factor family member GABPα/GABPβ1. Taken together with the fact that every MFNLP from a comparative study of over 500 LTR sequences from 42 patients contains a predicted binding site for RBF-2, our data suggest that the MFNLP is selected in vivo because it provides a duplicated RBF-2 cis element, which may limit transcription in monocytes and activated T cells.

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MultipleCis-acting DNA elements that regulate transcription of the adenovirus 12E1A gene

et al. 1992

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To delineate cis-acting elements for adenovirus (Ad) 12 E1A gene transcription, we transfected HeLa and NIH3T3 cells with DNAs having various deletions in the 5'-upstream region linked to the chloramphenicol acetyltransferase gene. Deletions in the regions between nucleotide (nt) positions 54 and 166, and 167 and 200, with respect to the left end of the viral genome at nt position 1, caused a two- to three-fold reduction in transcription. Transcription decreased to an almost undetectable level with loss of the region between nt positions 201 and 282. The effect of these mutations was almost consistent between both cell lines. The region between nt positions 77 and 94 stimulated transcription when situated upstream of the simian virus 40 early promoter in either orientation. Transcription was stimulated about ninefold in the presence of the DNA that encodes the product of the 13S, but not the 12S mRNA of the Ad12 E1A gene. These results indicate that transcription of the Ad12 E1A gene is regulated by multiple cis-acting elements and is stimulated by its own gene product.

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A novel cis-acting element that controls transcription of human immunodeficiency virus type 1 DNA, depending on cell type

Cited by 14 publications

References 52 publications

Differential role of long terminal repeat control elements for the regulation of basal and Tat-mediated transcription of the human immunodeficiency virus in stimulated and unstimulated primary human macrophages

Differential role of long terminal repeat control elements for the regulation of basal and Tat-mediated transcription of the human immunodeficiency virus in stimulated and unstimulated primary human macrophages

Naturally Occurring Human Immunodeficiency Virus Type 1 Long Terminal Repeats Have a Frequently Observed Duplication That Binds RBF-2 and Represses Transcription

MultipleCis-acting DNA elements that regulate transcription of the adenovirus 12E1A gene

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