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Publication : Sp5 induces the expression of Nanog to maintain mouse embryonic stem cell self-renewal.

First Author  Tang L Year  2017
Journal  PLoS One Volume  12
Issue  9 Pages  e0185714
PubMed ID  28961274 Mgi Jnum  J:246213
Mgi Id  MGI:5921569 Doi  10.1371/journal.pone.0185714
Citation  Tang L, et al. (2017) Sp5 induces the expression of Nanog to maintain mouse embryonic stem cell self-renewal. PLoS One 12(9):e0185714
abstractText  Activation of signal transducer and activator of transcription 3 (STAT3) by leukemia inhibitory factor (LIF) maintains mouse embryonic stem cell (mESC) self-renewal. Our previous study showed that trans-acting transcription factor 5 (Sp5), an LIF/STAT3 downstream target, supports mESC self-renewal. However, the mechanism by which Sp5 exerts these effects remains elusive. Here, we found that Nanog is a direct target of Sp5 and mediates the self-renewal-promoting effect of Sp5 in mESCs. Overexpression of Sp5 induced Nanog expression, while knockdown or knockout of Sp5 decreased the Nanog level. Moreover, chromatin immunoprecipitation (ChIP) assays showed that Sp5 directly bound to the Nanog promoter. Functional studies revealed that knockdown of Nanog eliminated the mESC self-renewal-promoting ability of Sp5. Finally, we demonstrated that the self-renewal-promoting function of Sp5 was largely dependent on its zinc finger domains. Taken together, our study provides unrecognized functions of Sp5 in mESCs and will expand our current understanding of the regulation of mESC pluripotency.
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