Different members of the Sp1 multigene family exert opposite transcritional regulation of the long terminal repeat of HIV-1

Abstract

Recently, a family of transcription factors structurally related to Sp1 has been described; thus, more than one activator may bind to the GC boxes present in a number of viral and cellular promoters. We have compared the transactivation potentials of Sp1, Sp3 and Sp4 proteins on the human immunodeficiency virus type 1 (HIV-1) promoter. The long terminal repeat (LTR) of HIV-1 contains three binding sites for the transcription factor Sp1 (GC boxes) which are involved in both basal and Tat-mediated transcriptional activation. Moreover, a cooperative interaction between NF-kappa B and Sp1 is required for HIV enhancer activation. We now demonstrate that Sp4 is an activator, while the Sp3 protein represses basal expression of HIV promoter. Remarkably, we found that over-expression of the transcription factor Sp3 was able to suppress Tat-mediated transactivation. These inhibitory effects of Sp3 correlate with its DNA binding activity, suggesting that Sp3 inhibition involves competition with Sp1 for occupancy of the GC boxes. Next, we have analyzed the role of different Sp1-related proteins in the stimulation of HIV-1 promoter in response to mitogens. We found that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, an interaction between NF-kappa B and the trans-acting domain (A domain) of Sp1 bound to an adjacent site must occur. We found that the cooperative interaction between NF-kappa B and Sp1 is highly specific, since neither Sp3 nor Sp4 is capable of cooperating with NF-kappa B.

Overlapping Sp1 and AP2 binding sites in a promoter element of the lens-specific MIP gene

“…A three zinc finger domain is highly conserved in members of this family, resulting in similar binding affinities to GC, GT and GA boxes. Sp1, Sp2 and Sp4 activate gene transcription, whereas Sp3 may function either as an activator or a repressor (49)(50)(51)(52)(53)(54)(55).…”

Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation

“…Sp3 has been reported to repress Sp1-mediated transcriptional activation, suggesting that it may be an inhibitory member of the Sp family of regulators (Majello et al, 1994;Hagen et al, 1995). However, the recent ®nding that Sp1 and Sp3 encode multiple proteins that di er in their capacity to stimulate or repress transcription, suggests that transcriptional control by the Sp family members is much more complex (Persengiev et al, 1995;Kennett et al, 1997;Dennig et al, 1997).…”

“…Two Sp3-related proteins of 78 kDa and 80 kDa, arising via internal translational initiation within Sp3 mRNA, have been described (Kennett et al, 1997). These two isoforms inhibit Spmediated transcription in vivo, while the initially described 110 kDa isoform behaves as a transcriptional activator (Majello et al, 1994). In the present study, we observed that all three isoforms of Sp3 are present in PC12 cells and speci®cally associate with the NGF-responsive region of the p21 promoter in both NGF-treated and exponentially-growing PC12 cells.…”

Kinetic analysis of Sp1-mediated transcriptional activation of the human DNA polymerase β promoter

“…Sp2, Sp3 and Sp4 are Sp1-related proteins. These proteins, like Sp1, are ubiquitously expressed, are glutamine-and serine/threonine-rich, and have similar DNA-binding speci®city, but display di erential e ects on the gene regulation (Hagen et al, 1992Kingsley and Winoto, 1992;Majello et al, 1994;Dennig et al, 1995). Among these, Sp1 is a highly studied factor and is known to activate many GC-box-containing viral and cellular promoters Tjian, 1983a,b, 1985;Gidoni et al, 1985).…”