RRC ID 76879
Author Okamoto K, Fujita H, Okada Y, Shinkai S, Onami S, Abe K, Fujimoto K, Sasaki K, Shioi G, Watanabe TM.
Title Single-molecule tracking of Nanog and Oct4 in living mouse embryonic stem cells uncovers a feedback mechanism of pluripotency maintenance.
Journal EMBO J
Abstract Nanog and Oct4 are core transcription factors that form part of a gene regulatory network to regulate hundreds of target genes for pluripotency maintenance in mouse embryonic stem cells (ESCs). To understand their function in the pluripotency maintenance, we visualised and quantified the dynamics of single molecules of Nanog and Oct4 in a mouse ESCs during pluripotency loss. Interestingly, Nanog interacted longer with its target loci upon reduced expression or at the onset of differentiation, suggesting a feedback mechanism to maintain the pluripotent state. The expression level and interaction time of Nanog and Oct4 correlate with their fluctuation and interaction frequency, respectively, which in turn depend on the ESC differentiation status. The DNA viscoelasticity near the Oct4 target locus remained flexible during differentiation, supporting its role either in chromatin opening or a preferred binding to uncondensed chromatin regions. Based on these results, we propose a new negative feedback mechanism for pluripotency maintenance via the DNA condensation state-dependent interplay of Nanog and Oct4.
Pages e112305
Published 2023-8-23
DOI 10.15252/embj.2022112305
PMID 37609947
PMC PMC10505915
MeSH Animals Cell Differentiation Chromatin / genetics Feedback Mice Mouse Embryonic Stem Cells* Single Molecule Imaging*
IF 9.889
Human and Animal Cells E14tg2a(AES0135)
Mice RBRC06037