Pwp1 Is Required for the Differentiation Potential of Mouse Embryonic Stem Cells through Regulating Stat3 Signaling. Mus musculus

We show that periodic tryptophan protein 1(Pwp1), a WD-40 repeat-containing protein associated with histone H4 modification, is required for the exit of mES cells from the pluripotent state into all lineages. Knockdown of Pwp1 does not affect mES cell proliferation, self-renewal or apoptosis. However, knockdown of Pwp1 impairs the differentiation potential of mES cells both in vitro and in vivo. The PWP1 ChIP-seq results revealed that the PWP1-occupied regions were marked with significant levels of H4K20me3. Moreover, Pwp1 and H4K20me3 bind to the same sites in the upstream region of Stat3. Knockdown of Pwp1 decreases the binding of H4K20me3 to the upstream region of Stat3 gene and upregulates the expression of Stat3. Furthermore, Pwp1 knockdown(KD) mES cells recover their differentiation potential through suppressing the expression of Stat3 or inhibiting the tyrosine phosphorylation of STAT3. Together, our results suggest that Pwp1 plays important roles in the differentiation potential of mES cells. Overall design: Examination of Pwp1 binding sites in mouse embryonic stem cells