TY - JOUR
T1 - Repression of kit expression by Plzf in germ cells
AU - Filipponi, Doria
AU - Hobbs, Robin M.
AU - Ottolenghi, Sergio
AU - Rossi, Pellegrino
AU - Jannini, Emmanuele A.
AU - Pandolfi, Pier Paolo
AU - Dolci, Susanna
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34748862280&partnerID=8YFLogxK
U2 - 10.1128/MCB.00479-07
DO - 10.1128/MCB.00479-07
M3 - Article
C2 - 17664282
AN - SCOPUS:34748862280
SN - 0270-7306
VL - 27
SP - 6770
EP - 6781
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 19
ER -