Data from: Oct4 redox sensitivity potentiates reprogramming and differentiation

The transcription factor Oct4/Pou5f1 is a component of the regulatory
circuitry governing pluripotency and is widely used to induce pluripotency
from somatic cells. Here we use domain swapping and mutagenesis to study
Oct4’s reprogramming ability, identifying a redox-sensitive DNA binding
domain cysteine residue (Cys48) as a key determinant of reprogramming and
differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition
of DNA binding activity and promotes oxidation-mediated protein
ubiquitylation. Pou5f1C48S point mutation has little effect on
undifferentiated embryonic stem cells (ESCs), but upon retinoic acid (RA)
treatment causes retention of Oct4 expression, deregulated gene expression
and aberrant differentiation. Pou5f1C48S ESCs also form less
differentiated teratomas and contribute poorly to adult somatic tissues.
Finally, we describe Pou5f1C48S(Janky) mice, which in the homozygous
condition are severely developmentally restricted after E4.5. Rare animals
bypassing this restriction appear normal at birth but are sterile.
Collectively, these findings uncover a novel Oct4 redox mechanism involved
in both entry into and exit from pluripotency.