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Molecular and Cellular Biology, May 2002, p. 3488-3496, Vol. 22, No. 10
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.10.3488-3496.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Gene Control in Germinal Differentiation: Rnf6, a Transcription Regulatory Protein in the Mouse Sertoli Cell

Pascal Lopez, Frédérique Vidal, Luc Martin, Luis A. Lopez-Fernandez,,{dagger} Jean-François Rual, Barry S. Rosen, François Cuzin,* and Minoo Rassoulzadegan

Unité 470 de l'Institut National de la Santé et de la Recherche Médicale, Université de Nice, Nice, France

Received 19 November 2001/ Returned for modification 7 January 2002/ Accepted 25 January 2002

In mouse Sertoli cells, transcription of the Inha gene encoding the {alpha} subunit of inhibin, which acts locally as a tumor suppressor, is down-regulated in tumors and in normal cells during aging. Previous studies suggested that regulation of Inha transcription involves the binding of a protein(s) to a repeat of the GGGGC motif in the promoter. Expression screening identified a cDNA encoding a protein that binds this sequence. Of the RING-H2 family, it is the mouse homologue of a human protein of unknown function, RNF6. The mouse gene, Rnf6, is predominantly expressed in two interacting cell types of the testis, Sertoli cells and pachytene spermatocytes. In Sertoli cells, it colocalizes with the PML and Daxx proteins in punctate nuclear bodies. In transient and stable transfectants, Rnf6 expression from a heterologous promoter increased the expression of reporter genes driven by the Inha promoter. In a Sertoli tumor cell line in which expression of both Inha and Rnf6 was reduced, reexpression of the latter restored the level of Inha while, concomitantly, the cells reverted to normal growth control in culture.

* Corresponding author. Mailing address: Unité INSERM U470, Faculté des Sciences, Université de Nice-Sophia Antipolis 06108, Nice Cédex 2, France. Phone: 33-492 07 64 11. Fax: 33-492 07 64 02. E-mail: cuzin{at}unice.fr.

{dagger} Present address: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Campus Universidad Autónoma, Madrid, Spain.

Molecular and Cellular Biology, May 2002, p. 3488-3496, Vol. 22, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.10.3488-3496.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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