Disease relevance of Sp1

• Two mutant Rb promoter-LacZ constructs were used to evaluate the importance of a single E2F site or a nearby activator (Sp1/Ets) site that is found mutated in low-penetrance retinoblastomas [1].
• Furthermore, the probe contains the Sp1 consensus binding sequence 5'CCGCCC3', in addition to the MRE consensus sequence, 5'TGCAC3', and we show that a Simian Virus 40 DNA fragment which contains six Sp1 binding sites did not bind p108 nor did it compete for the protein(s) interacting with MREd in a DNA footprinting assay [2].
• Surprisingly, vehicle-treated -/- mice displayed fibrosis and increased Sp1, skeletal actin, Nkx2.5, and GATA-4 expression without hypertrophy [3].
• Using a fragment spanning the region from nt -174 to +70 of the Ahr promoter, we found that four regions corresponding to four Sp1 sites were protected from DNase I digestion using nuclear extracts from MLE-12 (lung), F9 (embryonal carcinoma), Hepa-1 (hepatoma), and 41-5a (epidermal) cells [4].
• Analysis of restriction fragment length polymorphisms in recombinant inbred, congenic, and interspecific backcross mice using human and mouse cDNA probes demonstrated that Sp1-1 is a single gene closely linked to the mammary tumor virus integration site-1 (Int-1) on the distal end of chromosome 15 [5].

Psychiatry related information on Sp1

• Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease [6].

High impact information on Sp1

• We demonstrate that both gene-specific activator protein Sp1 and selective components of the core transcription apparatus, including TFIID and TFIIF, are direct targets inhibited by mutant htt in a polyglutamine-dependent manner [7].
• However, the expression of the methyl-CpG-binding protein MeCP2 is greatly reduced in Sp1-/- embryos [8].
• In Sp1-/- embryos, the expression of many putative target genes, including cell cycle-regulated genes, is not affected, CpG islands remain methylation free, and active chromatin is formed at the globin loci [8].
• Moreover, it has been suggested that Sp1 is linked to the maintenance of methylation-free CpG islands, the cell cycle, and the formation of active chromatin structures [8].
• Sp1-/- embryos are retarded in development, show a broad range of abnormalities, and die around day 11 of gestation [8].

Chemical compound and disease context of Sp1

• RESULTS: Tolfenamic acid and structurally related biaryl derivatives induced degradation of Sp1, Sp3, and Sp4 in pancreatic cancer cells [9].
• The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements [10].
• Involvement of Ets, rel and Sp1-like proteins in lipopolysaccharide-mediated activation of the HIV-1 LTR in macrophages [11].
• Mouse integrin alphav promoter is regulated by transcriptional factors Ets and Sp1 in melanoma cells [12].
• In the present study, we used a pancreatic cancer model to determine the role of Sp1 in the antitumor activity of celecoxib [13].

Biological context of Sp1

• Instead, it repressed Sp1-mediated transcriptional activation, suggesting that it is an inhibitory member of this family of regulatory factors [14].
• We found that the central region of c-Myc interacts with the zinc finger domain of Sp1 [15].
• Transcriptional regulation of the murine acetyl-CoA synthetase 1 gene through multiple clustered binding sites for sterol regulatory element-binding proteins and a single neighboring site for Sp1 [16].
• Analysis of the transcriptional activity of fragments of the SERCA3 promoter showed the existence of a minimal promoter region located between bases -97 and +153 that contains one ETS-binding site (EBS) and two Sp1 elements that are essential for basal transcription [17].
• Interestingly, EGR-1 is shown to down-regulate the transcription of its own gene expression, whereas Sp1 activated Egr-1 gene expression [18].

Anatomical context of Sp1

• To provide a genetic correlation for Sp1 activity in this system, a cell line homozygous for a targeted truncation of the Sp1 gene was derived and examined [19].
• In corroboration, efficient promoter activity was restored in differentiated muscle cells by exogenous expression of Sp1 and Sp3 [20].
• Basal transcription of the mouse sarco(endo)plasmic reticulum Ca2+-ATPase type 3 gene in endothelial cells is controlled by Ets-1 and Sp1 [17].
• Endogenous Sp1 and Sp3 proteins were detected only in myoblasts and not in myotubes, which indicates that the lack of these factors causes down-regulation of the Dp71 promoter activity in differentiated cells [20].
• EMSA analyses of a composite Egr/NF-AT site showed recruitment of Sp1 to this site in Th2 cells, but not in Th1 cells [21].

Associations of Sp1 with chemical compounds

• Coimmunoprecipitation and glutathione S-transferase pull-down experiments demonstrate that c-Myc may form complexes with Sp1/Sp3 [15].
• Moreover, the ability of estradiol to reverse TGF-beta1-stimulated type IV collagen synthesis is mediated by down-regulating CK2 activity, which ultimately limits the availability of unbound Sp1 to activate gene transcription [22].
• We identified a promoter region where cooperation between Ap1 and Sp1 elements was essential for TSA-induced cx43 transcription [23].
• We previously showed, using P19 cells as a model system, that the lamin A/C promoter has a retinoic acid-responsive element (L-RARE), and that Sp1 and Sp3 bind the CACCC box of the L-RARE [24].
• Parthenolide and mithramycin A, inhibitors of NF-kappaB and Sp1, respectively, abolished CML-induced MCP-1 gene expression in a dose-dependent manner [25].

Physical interactions of Sp1

• Chromatin immunoprecipitations used to analyze factor assembly and histone acetylation at the distal and proximal regions showed that Sp1 binding to and histone acetylation of the proximal region was dependent on NF-kappaB p65 [26].
• We conclude that Sp1 binding to the CT alpha proximal promoter is necessary to enhance transcription during the S phase [27].
• These results show that a metal regulatory element of the mouse MT-1 gene interacts specifically with a nuclear protein of Mr 108,000 and that this protein is distinct from the transcription factor Sp1 [2].
• Protein kinase casein kinase II (CK2) phosphorylates Egr-1 and prevents its binding to Sp1 [22].
• Collectively, our data suggest that Sp1 binds to the claudin-19 promoter region and is responsible for its expression in the kidney cell lines in vitro [28].

Enzymatic interactions of Sp1

• Sp1 binds in a phosphorylated state to the CTalpha promoter [29].

Regulatory relationships of Sp1

• Inhibition of Sp1 expression by RNA interference abolished the enhanced expression of CT alpha [27].
• Communication between NF-kappa B and Sp1 controls histone acetylation within the proximal promoter of the monocyte chemoattractant protein 1 gene [26].
• These results suggest that basal Ahr expression may be regulated by the expression and distribution of Sp1-like factors [4].
• Sp3 is a ubiquitously expressed human transcription factor closely related to Sp1 and Sp4 [14].
• Sp2 represses Sp1- and Sp3-driven transcription in Drosophila SL2 cells, but stimulates transcription in C3H10T1/2 mammalian cells [30].

Other interactions of Sp1

• Antibody "supershift" studies demonstrated that members of the Sp (Sp1, Sp3) and nuclear hormone receptor [chicken ovalbumin upstream promoter transcription factor (COUP-TF)/erbA-related protein 3] families interact with the pressure overload-responsive unit [31].
• This region contains multiple Sp1-binding sites and a potential initiator element, but no canonical Myc DNA-binding sites [15].
• Furthermore, transactivation of the -97/+301 promoter fragment by Ets-1 requires the presence of both the EBS and Sp1 sites, suggesting an interaction of the transcription factors on the gene promoter [17].
• Activation of CTP:phosphocholine cytidylyltransferase alpha expression during the S phase of the cell cycle is mediated by the transcription factor Sp1 [27].
• Sequencing of the 5'-flanking region also revealed potential cis-acting elements for multiple transcriptional regulatory factors including Sp1, zif268, Ets, CREB, and PuF sites [32].

Analytical, diagnostic and therapeutic context of Sp1

• Point mutation analysis and mobility shift assays showed that the sequence located between -54 and -37 is a functional Sp1-like transcription element [33].
• DNA affinity precipitation and chromatin immunoprecipitation assays indicated that binding of Sp1 and Sp3 to this consensus site was increased in B104-1-1 cells [34].
• Electrophoretic mobility shift assay and immunoprecipitation/Western studies indicated that the nuclear complex formed using the -66/-42 oligonucleotide contained both Sp1/Sp3 and Smad proteins [35].
• Consistently with the lower hINV promoter activity, immunoblotting studies indicate that Sp1 protein levels are lower in 3T3 and HEK-293 cells than in human epidermal keratinocytes [36].
• RAGE, phosphorylation of mitogen-activated protein kinases, nuclear factor (NF)-kappaB, c-Jun and Sp1 were studied using western blotting and immunocytochemistry [25].

References