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Science 9 May 1986:
Vol. 232. no. 4751, pp. 755 - 759
DOI: 10.1126/science.3008338
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Articles

Science, Vol 232, Issue 4751, 755-759
Copyright © 1986 by American Association for the Advancement of Science

articles

Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1

KA Jones, JT Kadonaga, PA Luciw, and R Tjian

The nature and position of transcriptional control elements responsible for the expression of genes encoded by the retrovirus associated with acquired immune deficiency syndrome (AIDS) have not been precisely defined. In this study it is shown that the mammalian Sp1 transcription factor binds to promoter sequences within the AIDS retrovirus long terminal repeat (LTR) and activates RNA synthesis five- to eightfold in reconstituted reactions in vitro. Experiments in which regions of DNA were protected from added reagents by specifically bound proteins (footprinting) indicated that the upstream promoter region of the AIDS virus LTR lies between -45 and -77 (relative to the RNA start site, +1) and contains three tandem, closely spaced SP1 binding sites of variable affinity. Base-substitution mutations targeted to one or all three Sp1 binding sites were found both to eliminate the binding of Sp1 and to cause up to a tenfold reduction in transcriptional efficiency in vitro. These findings suggest that one important component of the AIDS virus transcriptional control region interacts with a cellular transcription factor, Sp1, and that this factor must function in conjunction with transcriptional elements located downstream of the RNA cap site to mediate the response of the LTR to viral trans-activation.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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R. M. Oguariri, T. W. Brann, and T. Imamichi (2007)
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Tissue-specific regulation of ubiquitin (UbC) transcription by glucocorticoids: in vivo and in vitro analyses.
A. C. Marinovic, B. Zheng, W. E. Mitch, and S. R. Price (2007)
Am J Physiol Renal Physiol 292, F660-F666
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Human immunodeficiency virus type 1 Tat prevents dephosphorylation of Sp1 by TCF-4 in astrocytes.
A. Rossi, R. Mukerjee, P. Ferrante, K. Khalili, S. Amini, and B. E. Sawaya (2006)
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A Soluble Factor Secreted by an HIV-1-Resistant Cell Line Blocks Transcription through Inactivating the DNA-Binding Capacity of the NF-{kappa}B p65/p50 Dimer.
A. Lesner, Y. Li, J. Nitkiewicz, G. Li, A. Kartvelishvili, M. Kartvelishvili, and M. Simm (2005)
J. Immunol. 175, 2548-2554
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Artificial Zinc Finger Fusions Targeting Sp1-binding Sites and the trans-Activator-responsive Element Potently Repress Transcription and Replication of HIV-1.
Y.-S. Kim, J.-M. Kim, D.-L. Jung, J.-E. Kang, S. Lee, J. S. Kim, W. Seol, H.-C. Shin, H. S. Kwon, C. Van Lint, et al. (2005)
J. Biol. Chem. 280, 21545-21552
   Abstract »    Full Text »    PDF »
COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene transcription in human microglial cells.
C. Marban, L. Redel, S. Suzanne, C. Van Lint, D. Lecestre, S. Chasserot-Golaz, M. Leid, D. Aunis, E. Schaeffer, and O. Rohr (2005)
Nucleic Acids Res. 33, 2318-2331
   Abstract »    Full Text »    PDF »
Attenuation of HIV-1 Replication in Primary Human Cells with a Designed Zinc Finger Transcription Factor.
D. J. Segal, J. Goncalves, S. Eberhardy, C. H. Swan, B. E. Torbett, X. Li, and C. F. Barbas III (2004)
J. Biol. Chem. 279, 14509-14519
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Regulation of HIV-1 gene transcription: from lymphocytes to microglial cells.
O. Rohr, C. Marban, D. Aunis, and E. Schaeffer (2003)
J. Leukoc. Biol. 74, 736-749
   Abstract »    Full Text »    PDF »
The Apical Loop of the HIV-1 TAR RNA Hairpin Is Stabilized by a Cross-loop Base Pair.
T. Kulinski, M. Olejniczak, H. Huthoff, L. Bielecki, K. Pachulska-Wieczorek, A. T. Das, B. Berkhout, and R. W. Adamiak (2003)
J. Biol. Chem. 278, 38892-38901
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Tat and Trans-activation-responsive (TAR) RNA-independent Induction of HIV-1 Long Terminal Repeat by Human and Murine Cyclin T1 Requires Sp1.
V. S. R. K. Yedavalli, M. Benkirane, and K.-T. Jeang (2003)
J. Biol. Chem. 278, 6404-6410
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Sp1 and AP2 regulate but do not constitute TATA-less human TAFII55 core promoter activity.
T. Zhou and C.-M. Chiang (2002)
Nucleic Acids Res. 30, 4145-4157
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HIV-1 Tat Protein-mediated Transactivation of the HIV-1 Long Terminal Repeat Promoter Is Potentiated by a Novel Nuclear Tat-interacting Protein of 110 kDa, Tip110.
Y. Liu, J. Li, B. O. Kim, B. S. Pace, and J. J. He (2002)
J. Biol. Chem. 277, 23854-23863
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Ubiquitin (UbC) Expression in Muscle Cells Is Increased by Glucocorticoids through a Mechanism Involving Sp1 and MEK1.
A. C. Marinovic, B. Zheng, W. E. Mitch, and S. R. Price (2002)
J. Biol. Chem. 277, 16673-16681
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Sp1 Transcriptional Activity Is Up-regulated by Phosphatase 2A in Dividing T Lymphocytes.
I. Lacroix, C. Lipcey, J. Imbert, and B. Kahn-Perles (2002)
J. Biol. Chem. 277, 9598-9605
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Diversity of mosaic structures and common ancestry of human immunodeficiency virus type 1 BF intersubtype recombinant viruses from Argentina revealed by analysis of near full-length genome sequences.
M. M. Thomson, E. Delgado, I. Herrero, M. L. Villahermosa, E. Vazquez-de Parga, M. T. Cuevas, R. Carmona, L. Medrano, L. Perez-Alvarez, L. Cuevas, et al. (2002)
J. Gen. Virol. 83, 107-119
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Selected base sequence outside the target binding site of zinc finger protein Sp1.
M. Nagaoka, Y. Shiraishi, and Y. Sugiura (2001)
Nucleic Acids Res. 29, 4920-4929
   Abstract »    Full Text »    PDF »
NF{kappa}B and Sp1 Elements Are Necessary for Maximal Transcription of Toll-like Receptor 2 Induced by Mycobacterium avium.
T. Wang, W. P. Lafuse, and B. S. Zwilling (2001)
J. Immunol. 167, 6924-6932
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Latency-Associated Nuclear Antigen Encoded by Kaposi's Sarcoma-Associated Herpesvirus Interacts with Tat and Activates the Long Terminal Repeat of Human Immunodeficiency Virus Type 1 in Human Cells.
T. S. Hyun, C. Subramanian, M. A. Cotter II, R. A. Thomas, and E. S. Robertson (2001)
J. Virol. 75, 8761-8771
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SURVEY AND SUMMARY A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter.
L. A. Pereira, K. Bentley, A. Peeters, M. J Churchill, and N. J. Deacon (2000)
Nucleic Acids Res. 28, 663-668
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The Nuclear Receptor Chicken Ovalbumin Upstream Promoter Transcription Factor Interacts with HIV-1 Tat and Stimulates Viral Replication in Human Microglial Cells.
O. Rohr, C. Schwartz, C. Hery, D. Aunis, M. Tardieu, and E. Schaeffer (2000)
J. Biol. Chem. 275, 2654-2660
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Functional Interactions between C/EBP, Sp1, and COUP-TF Regulate Human Immunodeficiency Virus Type 1 Gene Transcription in Human Brain Cells.
C. Schwartz, P. Catez, O. Rohr, D. Lecestre, D. Aunis, and E. Schaeffer (2000)
J. Virol. 74, 65-73
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Transactivation activity of the human cytomegalovirus IE2 protein occurs at steps subsequent to TATA box-binding protein recruitment.
J.-M. Kim, Y. Hong, K.-T. Jeang, and S. Kim (2000)
J. Gen. Virol. 81, 37-46
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M.-Z. Cui, M. S. Penn, and G. M. Chisolm (1999)
J. Biol. Chem. 274, 32795-32802
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An Upstream Element Containing an ETS Binding Site Is Crucial for Transcription of the Human Presenilin-1 Gene.
M. Pastorcic and H. K. Das (1999)
J. Biol. Chem. 274, 24297-24307
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Localization of regulatory protein binding sites in the proximal region of human myometrial connexin 43 gene.
C. O. Echetebu, M. Ali, M. G. Izban, L. MacKay, and R. E. Garfield (1999)
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USF/c-Myc Enhances, While Yin-Yang 1 Suppresses, the Promoter Activity of CXCR4, a Coreceptor for HIV-1 Entry.
M. Moriuchi, H. Moriuchi, D. M. Margolis, and A. S. Fauci (1999)
J. Immunol. 162, 5986-5992
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Genetic Instability of Live, Attenuated Human Immunodeficiency Virus Type 1 Vaccine Strains.
B. Berkhout, K. Verhoef, J. L. B. van Wamel, and N. K. T. Back (1999)
J. Virol. 73, 1138-1145
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Development of a Self-Inactivating Lentivirus Vector.
H. Miyoshi, U. Blomer, M. Takahashi, F. H. Gage, and I. M. Verma (1998)
J. Virol. 72, 8150-8157
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Cooperative Actions of HIV-1 Vpr and p53 Modulate Viral Gene Transcription.
B. E. Sawaya, K. Khalili, W. E. Mercer, L. Denisova, and S. Amini (1998)
J. Biol. Chem. 273, 20052-20057
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A Developmental Stage-Specific Promoter Directs Germline Transcription of D{beta}J{beta} Gene Segments in Precursor T Lymphocytes.
M. L. Sikes, R. J. Gomez, J. Song, and E. M. Oltz (1998)
J. Immunol. 161, 1399-1405
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Sequences Just Upstream of the Simian Immunodeficiency Virus Core Enhancer Allow Efficient Replication in the Absence of NF-kappa B and Sp1 Binding Elements.
S. Pohlmann, S. Floss, P. O. Ilyinskii, T. Stamminger, and F. Kirchhoff (1998)
J. Virol. 72, 5589-5598
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Identification and Characterization of a Tannic Acid-responsive Negative Regulatory Element in the Mouse Mammary Tumor Virus Promoter.
F. Uchiumi, T. Sato, and S.-i. Tanuma (1998)
J. Biol. Chem. 273, 12499-12508
   Abstract »    Full Text »    PDF »
Modulation of Sp1 Phosphorylation by Human Immunodeficiency Virus Type 1 Tat.
R. F. Chun, O. J. Semmes, C. Neuveut, and K.-T. Jeang (1998)
J. Virol. 72, 2615-2629
   Abstract »    Full Text »    PDF »
Functional Interference of Sp1 and NF-kappa B through the Same DNA Binding Site.
F. Hirano, H. Tanaka, Y. Hirano, M. Hiramoto, H. Handa, I. Makino, and C. Scheidereit (1998)
Mol. Cell. Biol. 18, 1266-1274
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Selection of peptides that functionally replace a zinc finger in the Sp1 transcription factor by using a yeast combinatorial library.
X. Cheng, J. L. Boyer, and R. L. Juliano (1997)
PNAS 94, 14120-14125
   Abstract »    Full Text »    PDF »
COUP-TF and Sp1 Interact and Cooperate in the Transcriptional Activation of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat in Human Microglial Cells.
O. Rohr, D. Aunis, and E. Schaeffer (1997)
J. Biol. Chem. 272, 31149-31155
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Activation of the HIV-1 Long Terminal Repeat by Nerve Growth Factor.
J. A. Recio and A. Aranda (1997)
J. Biol. Chem. 272, 26807-26810
   Abstract »    Full Text »    PDF »
Modulation of Transcription Factor Sp1 by cAMP-dependent Protein Kinase.
C. Rohlff, S. Ahmad, F. Borellini, J. Lei, and R. I. Glazer (1997)
J. Biol. Chem. 272, 21137-21141
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CCAAT/enhancer binding protein (C/EBP) sites are required for HIV-1 replication in primary macrophages but not CD4+ T cells.
A. J. Henderson and K. L. Calame (1997)
PNAS 94, 8714-8719
   Abstract »    Full Text »    PDF »
In Vitro Chromatin Assembly of the HIV-1 Promoter. ATP-DEPENDENT POLAR REPOSITIONING OF NUCLEOSOMES BY Sp1 AND NFkappa B.
P. Widlak, R. B. Gaynor, and W. T. Garrard (1997)
J. Biol. Chem. 272, 17654-17661
   Abstract »    Full Text »    PDF »
The Natural Product Hymenialdisine Inhibits Interleukin-8 Production in U937 Cells by Inhibition of Nuclear Factor-kappa B.
J. J. Breton and M. C. Chabot-Fletcher (1997)
J. Pharmacol. Exp. Ther. 282, 459-466
   Abstract »    Full Text »
Structures of Zinc Finger Domains from Transcription Factor Sp1. INSIGHTS INTO SEQUENCE-SPECIFIC PROTEIN-DNA RECOGNITION.
V. A. Narayan, R. W. Kriwacki, and J. P. Caradonna (1997)
J. Biol. Chem. 272, 7801-7809
   Abstract »    Full Text »    PDF »
Regulation of HIV-1 Long Terminal Repeats by Interaction of C/EBP(NF-IL6) and NF-kappa B/Rel Transcription Factors.
M. R. Ruocco, X. Chen, C. Ambrosino, E. Dragonetti, W. Liu, M. Mallardo, G. De Falco, C. Palmieri, G. Franzoso, I. Quinto, et al. (1996)
J. Biol. Chem. 271, 22479-22486
   Abstract »    Full Text »    PDF »
Constitutive Expression of the Gene for the Cell-specific p48 DNA-binding Subunit of Pancreas Transcription Factor 1in Cultured Cells Is under Control of Binding Sites for Transcription Factors Sp1 and alpha Cbf.
M. Knofler, A. Krapp, O. Hagenbuchle, and P. K. Wellauer (1996)
J. Biol. Chem. 271, 21993-22002
   Abstract »    Full Text »    PDF »
An NF-kappa B Site in the 5'-Untranslated Leader Region of the Human Immunodeficiency Virus Type 1Enhances the Viral Expression in Response to NF-kappa B-activating Stimuli.
M. Mallardo, E. Dragonetti, F. Baldassarre, C. Ambrosino, G. Scala, and I. Quinto (1996)
J. Biol. Chem. 271, 20820-20827
   Abstract »    Full Text »    PDF »
Cloning and Characterization of a Functional Promoter of the Rat pp120 Gene, Encoding a Substrate of the Insulin Receptor Tyrosine Kinase.
S. M. Najjar, Y. R. Boisclair, Z. T. Nabih, N. Philippe, Y. Imai, Y. Suzuki, D.-S. Suh, and G. T. Ooi (1996)
J. Biol. Chem. 271, 8809-8817
   Abstract »    Full Text »    PDF »
Identification of a Group of Cellular Cofactors That Stimulate the Binding of RNA Polymerase II and TRP-185 to Human Immunodeficiency Virus 1 TAR RNA.
F. Wu-Baer, W. S. Lane, and R. B. Gaynor (1996)
J. Biol. Chem. 271, 4201-4208
   Abstract »    Full Text »    PDF »
Interaction of Virion Protein Vpr of Human Immunodeficiency Virus Type 1 with Cellular Transcription Factor Sp1 and trans-Activation of Viral Long Terminal Repeat.
L. Wang, S. Mukherjee, F. Jia, O. Narayan, and L.-J. Zhao (1995)
J. Biol. Chem. 270, 25564-25569
   Abstract »    Full Text »    PDF »
A Regulatory Element in the Human Interleukin 2 Gene Promoter Is a Binding Site for the Zinc Finger Proteins Sp1 and EGR-1.
C. Skerka, E. L. Decker, and P. F. Zipfel (1995)
J. Biol. Chem. 270, 22500-22506
   Abstract »    Full Text »    PDF »
Major Histocompatibility Complex Class II-associated Invariant Chain Gene Expression Is Up-regulated by Cooperative Interactions of Sp1 and NF-Y.
K. L. Wright, T. L. Moore, B. J. Vilen, A. M. Brown, and , J. P.-Y. Ting (1995)
J. Biol. Chem. 270, 20978-20986
   Abstract »    Full Text »    PDF »
p53 and Sp1 Interact and Cooperate in the Tumor Necrosis Factor-induced Transcriptional Activation of the HIV-1 Long Terminal Repeat.
A. Gualberto and A. S. Baldwin , Jr. (1995)
J. Biol. Chem. 270, 19680-19683
   Abstract »    Full Text »    PDF »
Molecular Cloning of a New Interferon-induced Factor That Represses Human Immunodeficiency Virus Type 1 Long Terminal Repeat Expression.
C. Tissot and N. Mechti (1995)
J. Biol. Chem. 270, 14891-14898
   Abstract »    Full Text »    PDF »
Members of the Sp Transcription Factor Family Control Transcription from the Uteroglobin Promoter.
Jör. Dennig, G. Hagen, M. Beato, and G. Suske (1995)
J. Biol. Chem. 270, 12737-12744
   Abstract »    Full Text »    PDF »
Characterization of a GC-rich Region Containing Sp1 Binding Site(s) as a Constitutive Responsive Element of the alpha2(I) Collagen Gene in Human Fibroblasts.
T. Tamaki, K. Ohnishi, C. Hartl, E. C. LeRoy, and M. Trojanowska (1995)
J. Biol. Chem. 270, 4299-4304
   Abstract »    Full Text »    PDF »
The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function..
C D Southgate and M R Green (1991)
Genes & Dev. 5, 2496-2507
   Abstract »    PDF »
tat regulates binding of the human immunodeficiency virus trans-activating region RNA loop-binding protein TRP-185..
F Wu, J Garcia, D Sigman, and R Gaynor (1991)
Genes & Dev. 5, 2128-2140
   Abstract »    PDF »
Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism..
E Pascal and R Tjian (1991)
Genes & Dev. 5, 1646-1656
   Abstract »    PDF »
DNA looping between sites for transcriptional activation: self-association of DNA-bound Sp1..
W Su, S Jackson, R Tjian, and H Echols (1991)
Genes & Dev. 5, 820-826
   Abstract »    PDF »
Synergy between HIV-1 Tat and adenovirus E1A is principally due to stabilization of transcriptional elongation..
M F Laspia, A P Rice, and M B Mathews (1990)
Genes & Dev. 4, 2397-2408
   Abstract »    PDF »
Molecular targets for AIDS therapy.
H Mitsuya, R Yarchoan, and S Broder (1990)
Science 249, 1533-1544
   Abstract »    PDF »
SV40 stimulates expression of the transacting factor Sp1 at the mRNA level..
J D Saffer, S P Jackson, and S J Thurston (1990)
Genes & Dev. 4, 659-666
   Abstract »    PDF »
Inhibition of DNA binding proteins by oligonucleotide-directed triple helix formation.
L. Maher 3rd, B Wold, and P. Dervan (1989)
Science 245, 725-730
   Abstract »    PDF »
Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines.
G Poli, J. Orenstein, A Kinter, T. Folks, and A. Fauci (1989)
Science 244, 575-577
   Abstract »    PDF »
In vitro formation of short RNA polymerase II transcripts that terminate within the HIV-1 and HIV-2 promoter-proximal downstream regions..
M G Toohey and K A Jones (1989)
Genes & Dev. 3, 265-282
   Abstract »    PDF »
Purification of the human histone H4 gene-specific transcription factors H4TF-1 and H4TF-2..
L Dailey, S B Roberts, and N Heintz (1988)
Genes & Dev. 2, 1700-1712
   Abstract »    PDF »
The Stases in Scientific and Literary Argument.
J. FAHNESTOCK and M. SECOR (1988)
Written Communication 5, 427-443
   Abstract »
Nef protein of HIV-1 is a transcriptional repressor of HIV-1 LTR.
N Ahmad and S Venkatesan (1988)
Science 241, 1481-1485
   Abstract »    PDF »
Regulation of HIV and HTLV gene expression..
H Varmus (1988)
Genes & Dev. 2, 1055-1062
   PDF »
Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters..
K A Jones, P A Luciw, and N Duchange (1988)
Genes & Dev. 2, 1101-1114
   Abstract »    PDF »
Retroviruses.
H Varmus (1988)
Science 240, 1427-1435
   Abstract »    PDF »
Constitutive and metal-inducible protein:DNA interactions at the mouse metallothionein I promoter examined by in vivo and in vitro footprinting..
P R Mueller, S J Salser, and B Wold (1988)
Genes & Dev. 2, 412-427
   Abstract »    PDF »
Both basal and ontogenic promoter elements affect the timing and level of expression of a sea urchin H1 gene during early embryogenesis..
Z C Lai, R Maxson, and G Childs (1988)
Genes & Dev. 2, 173-183
   Abstract »    PDF »
Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I.
M Siekevitz, S. Josephs, M Dukovich, N Peffer, F Wong-Staal, and W. Greene (1987)
Science 238, 1575-1578
   Abstract »    PDF »
The major late transcription factor binds to and activates the mouse metallothionein I promoter..
R W Carthew, L A Chodosh, and P A Sharp (1987)
Genes & Dev. 1, 973-980
   Abstract »    PDF »
Distinct factors with Sp1 and NF-A specificities bind to adjacent functional elements of the human U2 snRNA gene enhancer..
M Ares, J S Chung, L Giglio, and A M Weiner (1987)
Genes & Dev. 1, 808-817
   Abstract »    PDF »
Protein-DNA interactions in vivo upstream of a cell cycle-regulated human H4 histone gene.
U Pauli, S Chrysogelos, G Stein, J Stein, and H Nick (1987)
Science 236, 1308-1311
   Abstract »    PDF »
Expression and characterization of the trans-activator of HTLV-III/LAV virus.
C. Wright, B. Felber, H Paskalis, and G. Pavlakis (1986)
Science 234, 988-992
   Abstract »    PDF »
Purification and biochemical characterization of the promoter-specific transcription factor, Sp1.
M. Briggs, J. Kadonaga, S. Bell, and R Tjian (1986)
Science 234, 47-52
   Abstract »    PDF »
Transactivation of Naturally Occurring HIV-1 Long Terminal Repeats by the JNK Signaling Pathway. THE MOST FREQUENT NATURALLY OCCURRING LENGTH POLYMORPHISM SEQUENCE INTRODUCES A NOVEL BINDING SITE FOR AP-1 FACTORS.
P. Chen, E. Flory, A. Avots, B. W. M. Jordan, F. Kirchhoff, S. Ludwig, and U. R. Rapp (2000)
J. Biol. Chem. 275, 20382-20390
   Abstract »    Full Text »    PDF »
NF-Y and Sp1 Cooperate for the Transcriptional Activation and cAMP Response of Human Tissue Inhibitor of Metalloproteinases-2.
Z.-D. Zhong, K. Hammani, W. S. Bae, and Y. A. DeClerck (2000)
J. Biol. Chem. 275, 18602-18610
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)