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Molecular and Cellular Biology, October 2007, p. 6770-6781, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00479-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Repression of kit Expression by Plzf in Germ Cells

Doria Filipponi,¹ Robin M. Hobbs,² Sergio Ottolenghi,³ Pellegrino Rossi,¹ Emmanuele A. Jannini,⁴ Pier Paolo Pandolfi,² and Susanna Dolci^1*

Dipartimento di Sanità Pubblica e Biologia Cellulare, Università di Roma Tor Vergata, Rome, Italy,¹ Cancer Biology and Genetics Program, Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021,² Dipartimento di Biotecnologie e Bioscienze, Universit à Milano-Bicocca, Milan, Italy,³ Dipartimento di Medicina Sperimentale, Università dell'Aquila, L'Aquila, Italy⁴

Received 20 March 2007/ Returned for modification 30 April 2007/ Accepted 19 July 2007

Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion of the spermatogonial stem cell population. This is likely due to the deregulated expression of genes controlling the switch between spermatogonial self-renewal and differentiation. Here we show that Plzf directly represses the transcription of kit, a hallmark of spermatogonial differentiation. Plzf represses both endogenous kit expression and expression of a reporter gene under the control of the kit promoter region. A discrete sequence of the kit promoter, required for Plzf-mediated kit transcriptional repression, is bound by Plzf both in vivo and in vitro. A 3-bp mutation in this Plzf binding site abolishes the responsiveness of the kit promoter to Plzf repression. A significant increase in kit expression is also found in the undifferentiated spermatogonia isolated from Plzf^–/– mice. Thus, we suggest that one mechanism by which Plzf maintains the pool of spermatogonial stem cells is through a direct repression of kit expression.

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* Corresponding author. Mailing address: Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, Ed. E Nord, 00133 Rome, Italy. Phone: 390672596252. Fax: 390672596268. E-mail: dolci{at}uniroma2.it

Published ahead of print on 30 July 2007.

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Molecular and Cellular Biology, October 2007, p. 6770-6781, Vol. 27, No. 19
0270-7306/07/$08.00+0     doi:10.1128/MCB.00479-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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