The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor gene product p53 (original) (raw)
- Short Report
- Published: 26 May 1998
- Claire Montpellier3 na1,
- Eric Adriaenssens1,
- Séverine Lottin1,
- Lionel Dumont1,
- Violetta Iotsova3,
- Christian Lagrou3,
- Dominique Stéhelin3,
- Jean Coll3 &
- …
- Jean-Jacques Curgy1
Oncogene volume 16, pages 2395–2401 (1998)Cite this article
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Abstract
The developmentally regulated H19 gene displays several remarkable properties: expression of an apparently non-translated mRNA, genomic imprinting (maternal allele only expressed), relaxation of the imprinting and/or epigenetic lesions demonstrated in some tumors. Despite several observations after relaxation of imprinting status of the gene, data on trans and **cis**-acting factors required for the human H19 gene expression are still missing. As a first approach to address identification of factors involved in the regulation of the gene, we found that cells from a p53 antisense-transfected HeLa clone displayed increased amounts of H19 transcripts when compared to the non-transfected cells. Moreover, a HeLa clone stably transfected with a temperature sensitive (ts) 143 Ala p53 mutant exhibited temperature-dependent regulation of H19 expression. This preliminary indication of the repressing effect of the p53 protein on H19 expression has been confirmed by transient cotransfection experiments in HeLa cells, using luciferase surrogate constructs under the control of the 823 bp sequence immediately upstream of the transcription start point of the H19 gene, and different constructs containing sense, antisense or a ts 143 Ala mutant p53 cDNA. We observed an increase of H19 promoter-driven activity in transient cotransfections with the antisense p53 cDNA and the temperature sensitive mutant p53 at the non-permissive temperature, but a decrease with sense wild-type p53 cDNA. Furthermore, the cotransfection experiments were repeated in a cell line lacking endogenous p53. (Calu 6 cells) and the results provided additional evidence for a down regulation of the expression of the H19 gene by the p53 protein.
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Author notes
- Thierry Dugimont and Claire Montpellier: TD and CM made an equal contribution to this work
Authors and Affiliations
- Centre de Biologie Cellulaire, Unité `Dynamique des Cellules Embryonnaires et Cancéreuses' (EA 1033), SN3, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq cedex, 59655, France
Thierry Dugimont, Eric Adriaenssens, Séverine Lottin, Lionel Dumont & Jean-Jacques Curgy - Faculté des Sciences Jean Perrin, Université d'Artois, Lens cedex, 62307, France
Thierry Dugimont - Unité d'Oncologie Moléculaire, CNRS URA 1160, Institut Pasteur, rue Calmette, Lille cedex, 59019, France
Claire Montpellier, Violetta Iotsova, Christian Lagrou, Dominique Stéhelin & Jean Coll
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Dugimont, T., Montpellier, C., Adriaenssens, E. et al. The H19 TATA-less promoter is efficiently repressed by wild-type tumor suppressor gene product p53.Oncogene 16, 2395–2401 (1998). https://doi.org/10.1038/sj.onc.1201742
- Received: 30 June 1997
- Revised: 24 November 1997
- Accepted: 25 November 1997
- Published: 26 May 1998
- Issue Date: 07 May 1998
- DOI: https://doi.org/10.1038/sj.onc.1201742