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.

Repression of kit expression by Plzf in germ cells.

PANDOLFI DE RINALDIS, Pier Paolo;
2007-01-01

Abstract

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.
2007
27
6770
6781
http://dx.doi.org/10.1128/MCB.00479-07
http://mcb.asm.org/cgi/reprint/27/19/6770
Animals; Cell Differentiation; Cell Line; Consensus Sequence; Gene Expression Regulation; Genes; Reporter; Germ Cells; Humans; Kruppel-Like Transcription Factors; Male; Mice; Mice Transgenic; Octamer Transcription Factor-3; Promoter Regions; Genetic; Protein Binding; Proto-Oncogene Proteins c-kit; Spermatogonia
D. Filipponi;R. M. Hobbs;S. Ottolenghi;P. Rossi;E. A. Jannini;P. P. Pandolfi;S. Dolci
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/61458
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