SIRT1 Inhibits p53 but not NF-κB Transcriptional Activity during Differentiation of Mouse Embryonic Stem Cells into Embryoid Bodies.

Background And Objectives: SIRT1, a histone diacetylase, modify transactivation function of various transcription factor including p53 and NF-κB. p53 and NF-κB is involved in in vitro differentiation of mouse embryonic stem cells (mESC) into mouse embryoid body (mEB). These suggest that SIRT1 might affect in vitro differentiation of mESC into mEB by regulation of p53 and NF-κB.

Methods And Results: In this study we analyzed the effect of SIRT1 in in vitro differentiation of mESC into mEB using wild and SIRT1 knockout mESC. To examine SIRT1-specific gene in mESC, this study conducted microarray-based differential gene expression analysis between wild and SIRT1 knockout mESC. Comparing their gene expression patterns, this study determined a list of genes regulated by SIRT1. cDNA microarray data-set analysis revealed that genes associated with transcription and signal transduction are significantly modified in SIRT1 knockout mESC. cDNA microarray data-set analysis between mESC and EB in wild and SIRT1 showed that SIRT1 inhibits p53 signaling pathway but not affect NF-κB signaling pathway.

Conclusions: This study suggests that SIRT1 modify mESC differentiation by regulation of p53 transcriptional activity.