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. Additional upstream sequences up to position -3204 repressed promoter activity. Two independent repressor regions were identified and found to operate effectively in HeLa, COS-7 and HTR8/SVneo placental cells. More significantly, these negatively acting modules failed to repress a heterologous TATA-containing thymidine kinase promoter. Detailed transcriptional and DNA–protein analyses of the proximal repressor region (-605 to -254) revealed the presence of both negative and positive cis-acting elements. Disruption of the repressive functions resulted in an enhanced transcription of the reporter constructs. In conclusion, these results demonstrate that PSG-5 gene transcription is highly repressed by promoter-selective negative regulatory regions and the relief of repression allows enhanced PSG-5 gene transcription irrespective of the cell type. Furthermore, our findings suggest that PSG genes are expressed mainly through a derepression mechanism.
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Research Article|
August 23 2000
Transcription of genes encoding pregnancy-specific glycoproteins is regulated by negative promoter-selective elements
Graciela M. PANZETTA-DUTARI;
Graciela M. PANZETTA-DUTARI
1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina
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Nicolás P. KORITSCHONER;
Nicolás P. KORITSCHONER
1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina
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José L. BOCCO;
José L. BOCCO
1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina
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Rodrigo NORES;
Rodrigo NORES
1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina
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Catherine I. DUMUR;
Catherine I. DUMUR
1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina
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Luis C. PATRITO
Luis C. PATRITO
1
1Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ala Oeste, Ciudad Universitaria, 5000 Cordoba, Argentina
1To whom correspondence should be addressed (e-mail lpatrito@fcq.unc.edu.ar).
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Publisher: Portland Press Ltd
Received:
November 22 1999
Revision Received:
May 18 2000
Accepted:
June 23 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2000
2000
Biochem J (2000) 350 (2): 511–519.
Article history
Received:
November 22 1999
Revision Received:
May 18 2000
Accepted:
June 23 2000
Citation
Graciela M. PANZETTA-DUTARI, Nicolás P. KORITSCHONER, José L. BOCCO, Rodrigo NORES, Catherine I. DUMUR, Luis C. PATRITO; Transcription of genes encoding pregnancy-specific glycoproteins is regulated by negative promoter-selective elements. Biochem J 1 September 2000; 350 (2): 511–519. doi: https://doi.org/10.1042/bj3500511
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