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  Oct4 differentially regulates chromatin opening and enhancer transcription in pluripotent stem cells

Xiong, L., Tolen, E. A., Choi, J., Velychko, S., Caizzi, L., Velychko, T., et al. (2022). Oct4 differentially regulates chromatin opening and enhancer transcription in pluripotent stem cells. eLife, 11: e71533. doi:10.7554/eLife.71533.

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 Creators:
Xiong, L.1, Author           
Tolen, E. A., Author
Choi, J.1, Author           
Velychko, S., Author
Caizzi, L.1, Author           
Velychko, T.1, Author           
Adachi, K., Author
MacCarthy, C. M., Author
Lidschreiber, M.1, Author           
Cramer, P.1, Author           
Schöler, H. R., Author
Affiliations:
1Department of Molecular Biology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350224              

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 Abstract: The transcription factor Oct4 is essential for the maintenance and induction of stem cell pluripotency, but its functional roles are not fully understood. Here, we investigate the functions of Oct4 by depleting and subsequently recovering it in mouse embryonic stem cells (ESCs) and conducting a time-resolved multiomics analysis. Oct4 depletion leads to an immediate loss of its binding to enhancers, accompanied by a decrease in mRNA synthesis from its target genes that are part of the transcriptional network that maintains pluripotency. Gradual decrease of Oct4 binding to enhancers does not immediately change the chromatin accessibility but reduces transcription of enhancers. Conversely, partial recovery of Oct4 expression results in a rapid increase in chromatin accessibility, whereas enhancer transcription does not fully recover. These results indicate different concentration-dependent activities of Oct4. Whereas normal ESC levels of Oct4 are required for transcription of pluripotency enhancers, low levels of Oct4 are sufficient to retain chromatin accessibility, likely together with other factors such as Sox2.

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Language(s): eng - English
 Dates: 2021-06-222022-05-072022-05-27
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.7554/eLife.71533
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Funding organization : DFG (SFB860)
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Funding organization : DFB (SPP1935)
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Funding organization : DFG (EXC 2067/1-390729940)
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Funding program : Open Access Funding
Funding organization : Max Planck Society

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Title: eLife
Source Genre: Journal
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Pages: 28 Volume / Issue: 11 Sequence Number: e71533 Start / End Page: - Identifier: ISSN: 2050-084X