SV40 stimulates expression of the transacting factor Sp1 at the mRNA level.

Saffer, Jeffrey D.; Jackson, Stephen; Thurston, Sarah

doi:10.1101/gad.4.4.659

Cited by 123 publications

(82 citation statements)

References 44 publications

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“…This result is consistent with the observation that the recognition sequence for the members of the Sp family of transcription factors is highly variable, and it deviates¯exibly from the consensus Sp1 binding site (Kadonaga et al, 1986;Sa er et al, 1990). Unlike Sp1, Sp2 and Sp3 which are ubiquitously expressed in various tissues and cell types, Sp4 is known to be brain-speci®c (Kingsley and Winoto, 1991;Fischer et al, 1993;Hagen et al, 1992).…”

Section: Discussionsupporting

confidence: 84%

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

et al. 1997

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In this study, we have localized an enhancer element in the 5'-¯anking region of the HGF gene promoter and have identi®ed its functional transcriptional factors. Through transient transfection of NIH3T3 ®broblast cells and gel mobility shift assays, the functional binding site was localized to a short region (7318 to 7303 bp from the transcription start site) which has a CTCCC sequence. This motif is also conserved in the human HGF promoter and acts as a binding site for the Sp family of transcription factors. In the presence of NIH3T3 nuclear protein extracts, this enhancer region formed speci®c DNA-protein complexes which were totally abrogated by excess amounts of consensus Sp1 oligonucleotide. In gel mobility supershift assays, antiSp1 and anti-Sp3 antibodies speci®cally recognized these complexes as was evident by their slower migration. Sitespeci®c mutation of this binding motif resulted in total loss of Sp1 and Sp3 binding and a concomitant loss of enhancer function within the context of the HGF promoter. Furthermore, in transient cotransfection assays, overexpression of Sp1 and/or Sp3 stimulated HGF promoter activity independently and additively through binding to the Sp1 binding site in the HGF gene promoter region. DNaseI hypersensitive analysis of freshly isolated nuclei from NIH3T3 cells revealed that ®ve hypersensitive sites (HSS) are present within the 2 kb region immediately upstream of the HGF promoter. One of these sites was mapped to position 70.3 kb from the transcription start site. These data show that both Sp1 and Sp3 transcription factors upregulate HGF promoter activity by binding to the Sp1 binding site at position 7318 to 7303 bp in the HGF gene promoter.

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Section: Discussionsupporting

confidence: 84%

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

et al. 1997

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“…Additionally, there is evidence that Sp1 expression is regulated. Thus, Sp1 levels increase during SV40 infection of the CV1 cells (58). Furthermore, it has been reported that Sp1 expression varies greatly in different cell types and changes in Sp1 occur during development in vivo (59).…”

Section: Discussionmentioning

confidence: 92%

“…Recent studies indicate that Sp1 is a limiting factor in cultured cells and that overexpression of Sp1 increases expression from promoters containing GC-box elements (58). Additionally, there is evidence that Sp1 expression is regulated.…”

Section: Discussionmentioning

confidence: 99%

Myogenesis and MyoD Down-regulate Sp1

Viñals

Fandos

Santalucı́a

et al. 1997

Journal of Biological Chemistry

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Muscle cell differentiation caused a reduction of glucose transport, GLUT1 glucose transporter expression, and GLUT1 mRNA levels. A fragment of 2.1 kilobases of the rat GLUT1 gene linked to chloramphenicol acetyltransferase drove transcriptional activity in myoblasts, and differentiation caused a decrease in transcription. Transient transfection of 5 and 3 deletion constructs showed that the fragment ؊99/؊33 of the GLUT1 gene drives transcriptional activity of the GLUT1 gene and participates in the reduced transcription after muscle differentiation. Electrophoretic mobility shift assays showed the binding of Sp1 protein to the fragment ؊102/ ؊37 in the myoblast state but not in myotubes, and Sp1 was found to transactivate the GLUT1 promoter. Western blot analysis indicated that Sp1 was drastically down-regulated during myogenesis. Furthermore, the forced over-expression of MyoD in C3H10T1/2 cells mimicked the effects observed during myogenesis, Sp1 down-regulation and reduced transcriptional activity of the GLUT1 gene promoter.In all, these data suggest a regulatory model in which MyoD activation during myogenesis causes the down-regulation of Sp1, which contributes to the repression of GLUT1 gene transcription and, therefore, leads to the reduction in GLUT1 expression and glucose transport.

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“…Although Sp1 has primarily been considered a transcription factor for housekeeping genes, convincing evidence suggests that Sp1 is functionally regulated (31,32) and participates in cell type-specific gene expression (33)(34)(35). Moreover, Sp1 is regulated during development (36), is important for the expression of -globin in differentiating erythroid cells (37), and is highly expressed in areas of vasculogenesis such as the developing hearts of mouse embryos (36).…”

Section: In Vivo Analysis Of the Kdr/flk-1 Promoter By Lm-pcr-we Hypomentioning

confidence: 99%

Nuclear Protein Interactions with the Human KDR/flk-1 Promoter in Vivo

Patterson

Lee

et al. 1997

Journal of Biological Chemistry

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The endothelial cell type-specific tyrosine kinase KDR/flk-1 is a receptor for vascular endothelial growth factor and a critical regulator of endothelial cell growth and development. To study mechanisms of endothelial cell differentiation and gene regulation, we have analyzed the topology of the proximal promoter of human KDR/flk-1. A protected sequence between base pairs ؊110 and ؊25 was defined by in vitro DNase I footprinting analysis in human umbilical vein endothelial cells (HUVECs). Purified Sp1 alone produced similar protection, and electrophoretic mobility shift assays demonstrated that Sp1 was indeed the major nuclear protein binding to this region. Despite the cell type specificity of KDR/flk-1 expression, no cell type differences were observed in DNA-protein interactions in vitro. In contrast, in vivo footprinting assays demonstrated marked differences in core promoter interactions between cell types. Protection of Sp1 binding sites was observed in HUVECs by in vivo DNase I footprinting, whereas in human fibroblasts and HeLa cells a pattern consistent with nucleosomal positioning was observed. In vivo dimethylsulfate footprinting confirmed that DNA-protein interactions occurred within Sp1 elements in HUVECs but not in nonendothelial cells. It is possible that distant elements coordinate Sp1 binding and chromatin structure to regulate cell type-specific expression of KDR/flk-1.KDR/flk-1 is a membrane-bound receptor of the tyrosine kinase family with expression restricted predominantly to endothelial cells (1). KDR/flk-1 and a similar tyrosine kinase, flt-1, are receptors for the specific endothelial cell mitogen and angiogenic peptide vascular endothelial growth factor (VEGF) 1 (1-3). Both receptors are expressed early in murine development, with KDR/flk-1 appearing a full day earlier (day 7.0 -7.5 of the developing mouse embryo) than flt-1 (4, 5). Of the two, KDR/flk-1 has a wider pattern of expression among endothelial cell populations than does flt-1 (6). In addition, only KDR/flk-1 has been shown to autophosphorylate in the presence of VEGF (1), and signal transduction mechanisms downstream of the two receptors differ (7). These differences in expression and signaling suggest that the two receptors mediate different physiologic functions of VEGF in endothelial cell growth and angiogenesis.Recent studies in which the genes for the two VEGF receptors were deleted in mice by homologous recombination have provided critical data about KDR/flk-1 function (8, 9). In mice with homozygous deletions of flt-1, endothelial cells develop normally, but vessel formation is impaired, and lethality occurs at the midsomitic stages of development. In contrast, homozygous deletion of KDR/flk-1 also results in early embryo death (at day 8.5-9.5), but histologic examination reveals that embryonic endothelial cells are completely absent. Thus, KDR/ flk-1 appears to be upstream of flt-1 in the cascade of vascular development; moreover, the presence of KDR/flk-1 is absolutely required for the development of endothelial cel...

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SV40 stimulates expression of the transacting factor Sp1 at the mRNA level.

Cited by 123 publications

References 44 publications

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

Transcriptional regulation of the hepatocyte growth factor (HGF) gene by the Sp family of transcription factors

Myogenesis and MyoD Down-regulate Sp1

Nuclear Protein Interactions with the Human KDR/flk-1 Promoter in Vivo

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