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OCT4 and SOX2 Work as Transcriptional Activators in Reprogramming Human Fibroblasts
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In mouse embryonic fibroblasts (MEFs), OCT4 binds somatic enhancers during reprogramming and may initiate their inactivation, whereas in human fetal fibroblasts, OCT4 and SOX2 bind putative enhancers and remain bound in iPS cells.
“Specifically, in mouse embryonic fibroblasts (MEFs), OCT4 binds somatic enhancers during reprogramming and may initiate their inactivation, whereas in human fetal fibroblasts, OCT4 and SOX2 bind putative enhancers and remain bound in iPS cells.”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [82]
The Discussion (OCT4 and SOX2 work as activators during reprogramming; page unavailable) reports that Chronis et al. suggested OCT4 may initiate inactivation of pre-existing fibroblast enhancers, but does not identify those cells as MEFs. The Results (Putative enhancers at sites of bound transcription factors; page unavailable) confirm that OCT4 and SOX2 bind putative enhancers in day-5 human cells and iPS cells. The Discussion (Transcription factor repositioning; page unavailable) says most binding sites differ between those stages, so the claim is supported only if ‘remain bound’ means binding enhancers in iPS cells, not remaining at the same sites. (LLM, conf=0.82)
Experimental — accuracy not yet measuredDistinct mechanisms observed among combinations of OCT4 and SOX2 (without KLF4) versus OSK may explain the controversy regarding whether OSK mainly function as pioneer factors or bind readily open chromatin in early reprogramming, or both.
“The distinct mechanisms observed among combinations of OCT4 and SOX2 (without KLF4) versus OSK may explain the controversy regarding whether OSK mainly function as the pioneer factors or bind readily open chromatin in early reprogramming, or both 80,82,83,85 .”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [82]
The Results section (‘Putative enhancers at sites of bound transcription factors’; page unavailable) reports that OCT4 and SOX2 often bound sites where new putative enhancers formed, whereas KLF4-bound enhancers were almost all pre-existing. This supports a distinction between the factors in early reprogramming, but the paper does not compare an OCT4–SOX2 combination without KLF4 against OSK or establish that such a comparison explains the pioneer-factor controversy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredOSK factors interact with the genome and each other differently in mice than in human cells.
“OSK factors interact with the genome and each other differently in mice than in human cells [80][81][82] , complicating the design and interpretation of studies.”
From Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming (2023) · cites this paper as [82]
The Results (‘Changing locations of DNA bound factors’; page not available) describe OCT4 and SOX2 binding to DNA and co-binding in human cells. The paper does not compare those interactions—or KLF4’s—with mouse cells, so it does not support the claimed mouse–human difference. (LLM, conf=0.83)
Experimental — accuracy not yet measured
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Citations
Cites
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“02%), and that for human cells from older donors even lower (Maherali et al., 2008; Park et al., 2008; Paull et al., 2015; Rohani et al., 2014; Takahashi et al., 2007; Yu et al., 2007).”
BackgroundInfluentialCooperative Binding of Transcription Factors Orchestrates Reprogramming
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Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming
Cipriano, A., Moqri, M., Maybury-Lewis, S. Y., Rogers-Hammond, R., de Jong, T. A., Parker, A., Rasouli, S., Schöler, H. R., Sinclair, D. A., & Sebastiano, V. (2023) · Nature Aging · doi:10.1038/s43587-023-00539-2 · Cited by 66
Metadata
- Authors
- Narayan, S., Bryant, G., Shah, S., Berrozpe, G., & Ptashne, M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 20
- Issue
- 7
- Pages
- 1585-1596
- ISSN
- 2211-1247
- PMC
- PMC5648000
- Cited by
- 43
- References
- 6
- Language
- en
- Licence
- Funders
- NYSTEM (C029153, N09G-217, N11G-262)
- MSKCC Support Grant/Core Grant (P30 CA008748)
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