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Sp1 transcription factor OKDB#: 2363
 Symbols: SP1 Species: human
 Synonyms:  Locus: 12q13.13 in Homo sapiens


For retrieval of Nucleotide and Amino Acid sequences please go to: OMIM Entrez Gene
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General Comment The transcription factor Sp1 is a DNA-binding protein which interacts with a variety of gene promoters containing GC-box elements.

NCBI Summary: The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. Post-translational modifications such as phosphorylation, acetylation, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
General function DNA binding, Transcription factor
Comment Cathepsin L gene expression and promoter activation in rodent granulosa cells. Sriraman V,et al 2004 . The cysteine protease cathepsin L exhibits hormone-regulated expression during ovulation. In situ hybridization analyses of immature and pregnant mare serum gonadotropin-treated mouse and rat ovaries showed that cathepsin L expression in granulosa cells of small, growing follicles increased in periovulatory follicles after human chorionic gonadotropin stimulation. In the rat ovary, cathepsin L was also expressed in follicles with signs of atresia. To determine the molecular mechanisms that mediate the diverse regulation of this gene in granulosa cells, rat cathepsin L promoter-reporter constructs were analyzed by transient transfection assays in rat granulosa cells and EMSAs. A construct containing the transcriptional start site and -244 bp of upstream promoter sequence (-244/+33 bp) exhibited inducibility by forskolin, the phorbol ester phorbol myristate acetate, and an additive effect of both. Within this region, three functional specificity protein 1 (Sp1) sites, an overlapping early growth response protein-1 site, and a cAMP regulatory element-binding protein site were identified. Single or double mutants of the above-mentioned sites did not alter forskolin/phorbol myristate acetate inducibility of the promoter. Mutation of all three Sp1/specificity protein 3 (Sp3) sites, which also mutated the early growth response protein-1 site, reduced the promoter activation. Mutation of the cAMP regulatory element-binding protein site in the triple Sp1 mutant construct completely blocked the inducibility of the promoter. When these same constructs were transfected into MCF-7 human breast cancer cells or were cotransfected with an Sp1 expression vector in Drosophila SL2 cells, similar results were obtained. Collectively, the data document that three Sp1/specificity protein 3 binding GC-rich regions and a functional cAMP regulatory element constitute an important transcriptional regulatory complex for expression of the cathepsin L gene in rat granulosa cells.
Cellular localization Nuclear
Comment
Ovarian function Steroid metabolism
Comment Sp1 Regulates Steroidogenic Genes and LHCGR Expression in Primary Human Luteinized Granulosa Cells. Convissar S et al. (2019) Luteinizing hormone and human chorionic gonadotropin (hCG) bind to the luteinizing hormone/chorionic gonadotropin receptor (LHCGR). LHCGR is required to maintain corpus luteum function but the mechanisms involved in the regulation of LHCGR in human luteal cells remain incompletely understood. This study aimed to characterize the expression of LHCGR mRNA in primary human luteinized granulosa cells (hLGCs) obtained from patients undergoing in vitro fertilization and to correlate LHCGR expression with the response of hLGCs to hCG by assessing the expression of genes known to be markers of hCG actions. The results show that LHCGR expression is low in freshly isolated cells but recovers rapidly in culture and that hCG maintains LHCGR expression, suggesting a positive feedback loop. The activity of a LHCGR-LUC reporter increased in cells treated with hCG but not with follicle-stimulating hormone. Treatment with hCG also stimulated the expression of genes involved in steroidogenesis in a time-dependent manner. LHCGR promoter expression was found to be regulated by SP1, which we show is highly expressed in hLGCs. Moreover, SP1 inhibition prevented the stimulation of steroidogenic genes and the increase in LHCGR-LUC reporter activity by hCG. Finally, we provide evidence that a complex formed by SP1 and GATA4 may play a role in the maintenance of LHCGR expression. This report reveals the mechanisms involved in the regulation of the LHCGR and provides experimental data demonstrating that the proximal region of the LHCGR promoter is sufficient to drive the expression of this gene in primary hLGCs.//////////////////
Expression regulated by
Comment Involvement of Sp1 and SREBP-1a in Transcriptional Activation of the Low Density Lipoprotein-Receptor Gene by Insulin and Luteinizing Hormone in Cultured Porcine Granulosa-Luteal Cells. Sekar N, et al . Luteinizing hormone (LH) and insulin stimulate transcriptional activity of the porcine low density lipoprotein (LDL)-receptor promoter supraaddtively in primary cultures of granulosa-luteal cells. The mechanistic basis of this bihormonal interaction is unknown. Unlike the human, the pig LDL-R gene promoter has four imperfect repeats, which include two tandem upstream and one downstream putative Sp1/Sp3 binding sites and one canonical sterol-regulatory element (SRE) site between -255 to -139 bp 5'- upstream to the transcriptional start site. To assess the role of SRE binding protein (SREBP) in LDL-receptor gene regulation, swine granulosa-luteal cells were cotransfected with constitutively driven minigenes CMV/SREBP-1a or SREBP-2 and the pLDLR1076/luc promoter. SREBP-1a and SREBP-2 stimulated LDL-R gene transcription by 8- and 4-fold (both P < 0.01), respectively. LH alone augmented stimulation by SREBP-1 by 2-fold (P < 0.05). Conversely, cotransfection of a dominant-negative mutant form of SREBP-1a (lacking sequences for the N-terminal 90 amino acids) repressed basal and hormonally stimulated LDL-R promoter activity by > 80% (P < 0.01). The relevance of the SRE site in the LDL-receptor promoter was examined by mutation of the cognate -167 ATCACCCCATG -157 to -167 ATCACCgCATG -157 bp. This substitution decreased basal expression by 50% (P < 0.05) and LH and insulin/IGF-I-stimulated transcriptional activity by 80% and > 90% respectively (both P < 0.01). Mutations within each of the three flanking putative Sp1/Sp3 sites at - 216 TCCTCC -211, - 201 TCCTCC - 196 and - 151 TCCTCC -146 bp in the LDL-receptor gene promoter also reduced basal activity (by > 85%, P < 0.05) and hormonal responsiveness (by > 95%, P < 0.05). Electrophoretic gel mobility-shift assays (EMSA) using swine granulosa-luteal cell nuclear protein with specific antibody or recombinant SREBP-1a protein confirmed that presumptive SRE-1 and Sp1/Sp3 elements bind respective peptides. Motifs that putatively associate with Sp1/Sp3 appear to be important functionally, since mithramycin, an inhibitor of Sp1/Sp3 protein(s) binding, blocked hormonally induced LDL-receptor promoter expression by 80% (P <0.01). In conclusion, basal transcription and supraadditive stimulation of porcine LDL-receptor gene transcription by LH and insulin in granulosa-luteal cells requires SREBP-1a and Sp1/Sp3 binding elements.
Ovarian localization Granulosa, Luteal cells
Comment
Follicle stages Antral, Preovulatory
Comment
Phenotypes
Mutations 0 mutations
Genomic Region show genomic region
Phenotypes and GWAS show phenotypes and GWAS
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created: Jan. 31, 2004, 8:31 a.m. by: hsueh   email:
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last update: April 9, 2019, 2:17 p.m. by: hsueh    email:



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