Year: 2021
Type: article
Abstract: The pluripotency factor OCT4 is essential for the maintenance of naive 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. In addition, we find that NANOG is able to bind to the genome in the absence of OCT4, and this binding is in fact enhanced. Globally, however, the active enhancer-associated histone mark H3K27ac is depleted. Our work establishes that, while OCT4 is required for the maintenance of the naive transcription factor network, at a normal embryonic stem cell levels it antagonizes this network through inhibition of NANOG binding.
Source: Stem Cell Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Awards: Defining the mechanisms of induced pluripotency., Joint Wellcome and MRC Centre, ‘Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute’, G2127290718, Re-defining the paradigm of X-chromosome inactivation, G5446907700, G6831373058, Cambridge Stem Cell Institute, G7413708881, G8221906125, Deciphering and overcoming epigenetic erosion at imprinted loci in mouse and human naive pluripotent stem cells
OpenAlex ID: W3166702695