Journal
NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-11054-7
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Funding
- National Key Research and Development Program of China Stem Cell and Translational Research [2017YFA0105103, 2017YFA0105101]
- National Natural Science Foundation of China [31471238, 31771454, 31611130038, 31771424]
- Ministry of Science and Technology (MOST) of China [2016YFA0100700]
- 100 talent award of the Chinese Academy of Sciences
- Science and Technology Planning Projects of Guangdong Province, China [2014B030301058, 2016A050503038, 2017B030314056]
- Research Grants Council of Hong Kong General Research Fund (RGC/GRF) [17128918]
- Health and Medical Research Fund [06174006]
- Germany/Hong Kong Joint Research Scheme - Research Grants Council of Hong Kong [GHKU701/18]
- Germany/Hong Kong Joint Research Scheme - German Academic Exchange Service [GHKU701/18]
- Max Planck-GIBH Joint Center for Regenerative Biomedicine
- Science and Technology Planning Project of Guangdong Province [2014B020225002]
- Chinese Government Scholarship (CGS)
- University of the Chinese Academy of Sciences (UCAS)
- CAS-TWAS (Chinese Academy of Sciences-The World Academy of Sciences)
- UCAS (University of Chinese Academy of Science)
- Deutsche Forschungsgemeinschaft [ME4154/4-1]
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Oct4, along with Sox2 and Klf4 (SK), can induce pluripotency but structurally similar factors like Oct6 cannot. To decode why Oct4 has this unique ability, we compare Oct4-binding, accessibility patterns and transcriptional waves with Oct6 and an Oct4 mutant defective in the dimerization with Sox2 (Oct4(defSox2)). We find that initial silencing of the somatic program proceeds indistinguishably with or without Oct4. Oct6 mitigates the mesenchymal-to-epithelial transition and derails reprogramming. These effects are a consequence of differences in genome-wide binding, as the early binding profile of Oct4(defSox2) resembles Oct4, whilst Oct6 does not bind pluripotency enhancers. Nevertheless, in the Oct6-SK condition many otherwise Oct4-bound locations become accessible but chromatin opening is compromised when Oct4(defSox2) occupies these sites. We find that Sox2 predominantly facilitates chromatin opening, whilst Oct4 serves an accessory role. Formation of Oct4/Sox2 heterodimers is essential for pluripotency establishment; however, reliance on Oct4/Sox2 heterodimers declines during pluripotency maintenance.
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