Repression of kit expression by Plzf in germ cells.
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.
Filipponi
Doria
D
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, Ed E Nord, Rome, Italy.
Hobbs
Robin M
RM
Ottolenghi
Sergio
S
Rossi
Pellegrino
P
Jannini
Emmanuele A
EA
Pandolfi
Pier Paolo
PP
Dolci
Susanna
S
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D016384:Consensus Sequence; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D013093:Spermatogonia / Q000166:cytology / Q000502:physiology*
D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; D019009:Proto-Oncogene Proteins c-kit