Pregnancy-specific glycoproteins (PSGs) are major placental proteins thought to be essential for the maintenance of gestation. Little is known about the regulation of expression of the 11 genes encoding these proteins. It was previously demonstrated that Krüppel-like factor 6 (KLF6) and specific-protein 1 (Sp1) bind to conserved sequence within the PSG-5 gene promoter. Informatics analysis revealed the presence of one potential binding site for Krüppel-like factor 4 (KLF4), in the PSG-5 promoter, suggesting a potential transcriptional regulator role for KLF4. Using gene promoter-reporter transfections and X-ChIP assays, we demonstrated that KLF4 is an activator of the PSG-5 promoter by binding to a KLF consensus like binding which includes the Core Promoter Element region (-147/-140). Furthermore, we used previous data showing the binding of Sp1 transcription factor to a GT-box (-443/-437) and co-transfection assays with KLF4 and Sp1 to demonstrate the strong synergic activity of these two factors on the PSG-5 promoter.
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PSG gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins.
PLoS One
August 2013
Centro de Investigaciones en Bioquímica Clínica e Inmunología CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Background: Lysine acetylation is an important post-translational modification that plays a central role in eukaryotic transcriptional activation by modifying chromatin and transcription-related factors. Human pregnancy-specific glycoproteins (PSG) are the major secreted placental proteins expressed by the syncytiotrophoblast at the end of pregnancy and represent early markers of cytotrophoblast differentiation. Low PSG levels are associated with complicated pregnancies, thus highlighting the importance of studying the mechanisms that control their expression.
View Article and Find Full Text PDFActivation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1.
Biochem Biophys Res Commun
May 2006
INSERM U.384, Laboratoire de Biochimie, Faculté de Médecine, F-63000 Clermont-Ferrand, France.
Pregnancy-specific glycoproteins (PSGs) are major placental proteins thought to be essential for the maintenance of gestation. Little is known about the regulation of expression of the 11 genes encoding these proteins. It was previously demonstrated that Krüppel-like factor 6 (KLF6) and specific-protein 1 (Sp1) bind to conserved sequence within the PSG-5 gene promoter.
View Article and Find Full Text PDFTranscriptional control of the human pregnancy-specific glycoprotein 5 gene is dependent on two GT-boxes recognized by the ubiquitous specificity protein 1 (Sp1) transcription factor.
Placenta
January 2004
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre, Ciudad Universitaria, 5000 Córdoba, Argentina.
Pregnancy-specific glycoprotein 5 gene (PSG-5) belongs to the human pregnancy-specific glycoprotein family, encoded by eleven highly similar and transcriptionally active genes. High levels of PSG biosynthesis are restricted to the placenta syncytiotrophoblast and are essential for the maintenance of normal gestation in mammalian species. We have investigated here the nature of the transcription factors that recognize the FP1 (-455/-433) and the CPE (-147/-140) regulatory sequences that significantly contribute to basal PSG-5 promoter activity.
View Article and Find Full Text PDFTranscription of genes encoding pregnancy-specific glycoproteins is regulated by negative promoter-selective elements.
Biochem J
September 2000
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina.
The human pregnancy-specific glycoprotein (PSG) genes comprise a family of 11 highly conserved members whose expression is maximal in placental cells and marginal in other cell types. We have investigated here the molecular basis of PSG regulation by analysing a large regulatory region of the PSG-5 gene in cells that do and do not express these genes. The promoter region (-254 to -43), which does not contain a TATA-box, large GC-rich sequences or a classical initiator, was active in all cell types analysed.
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