Figure 1

Precise control of Oct4 expression at multiple levels. The chromatin modifier Paf1C increases Oct4 expression by relaxing the compact chromatin, while G9a adds a repressive mark and recruits heterochromatin protein 1 (HP1), leading to a compact chromatin configuration. Subsequently, Dnmt3a/b methylates the Oct4 promoter to permanently inactivate Oct4 expression. This process is enhanced by Cdk2ap1 interacting with Mbd3. At the transcription level, two sets of transcription factors and nuclear receptors function antagonistically: one set (including Esrrb, LRH-1, Oct4, Sox2 and Sall4) activates Oct4 expression, while the other set (including germ cell nuclear factor (GCNF) and Tr2) represses its expression. After transcription, Lin28 recruits RNA helicase A to promote the translation of Oct4 mRNA, while miRNAs (including miR-134 and miR-470) cause its decay. In addition, several post-translational modifications (such as ubiquitination (Ub), sumoylation and phosphorylation (P)) are added to the Oct4 protein after it is translated and influence the activity and stability of Oct4 proteins. SUMO, small ubiquitin-related modifier.