RT Journal Article
SR Electronic
T1 Auxin-degron system identifies immediate mechanisms of Oct4
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.09.21.306241
DO 10.1101/2020.09.21.306241
A1 Lawrence E Bates
A1 Mariana R P Alves
A1 José C R Silva
YR 2020
UL http://biorxiv.org/content/early/2020/09/22/2020.09.21.306241.abstract
AB The pluripotency factor Oct4 is essential for the maintenance of naïve pluripotent stem cells in vitro and in vivo. However, the specific role of Oct4 in this process remains unknown. Here, we developed a rapid protein-level Oct4 depletion system that demonstrates that the immediate downstream response to loss of Oct4 is reduced expression of key pluripotency factors. Our data show a requirement for Oct4 for the efficient transcription of several key pluripotency factors, and suggest that expression of trophectoderm markers is a subsequent event. Additionally, we find that Nanog is competent to bind to the genome in the absence of Oct4, and this binding is in fact enhanced. Globally, however, active enhancer associated histone mark H3K27ac is depleted. Our work establishes that while Oct4 is required for the maintenance of the naïve transcription factor network, at a normal ESC level it antagonises this network through inhibition of Nanog binding.Competing Interest StatementThe authors have declared no competing interest.