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| Item Type: | Article |
|---|---|
| Title: | FACT sets a barrier for cell fate reprogramming in Caenorhabditis elegans and human cells |
| Creators: |
Kolundzic, E.  ORCID: https://orcid.org/0000-0002-7811-3174, Ofenbauer, A. ORCID: https://orcid.org/0000-0003-0379-9105, Bulut, S.I., Uyar, B. ORCID: https://orcid.org/0000-0002-3170-4890, Baytek, G. ORCID: https://orcid.org/0000-0001-9731-9461, Sommermeier, A., Seelk, S. ORCID: https://orcid.org/0000-0002-3525-8859, He, M., Hirsekorn, A., Vucicevic, D. ORCID: https://orcid.org/0000-0002-1162-6709, Akalin, A. ORCID: https://orcid.org/0000-0002-0468-0117, Diecke, S. ORCID: https://orcid.org/0000-0002-5219-5992, Lacadie, S.A. ORCID: https://orcid.org/0000-0002-0893-5340 and Tursun, B. ORCID: https://orcid.org/0000-0001-7293-8629
|
| Abstract: | The chromatin regulator FACT (facilitates chromatin transcription) is essential for ensuring stable gene expression by promoting transcription. In a genetic screen using Caenorhabditis elegans, we identified that FACT maintains cell identities and acts as a barrier for transcription factor-mediated cell fate reprogramming. Strikingly, FACT's role as a barrier to cell fate conversion is conserved in humans as we show that FACT depletion enhances reprogramming of fibroblasts. Such activity is unexpected because FACT is known as a positive regulator of gene expression, and previously described reprogramming barriers typically repress gene expression. While FACT depletion in human fibroblasts results in decreased expression of many genes, a number of FACT-occupied genes, including reprogramming-promoting factors, show increased expression upon FACT depletion, suggesting a repressive function of FACT. Our findings identify FACT as a cellular reprogramming barrier in C. elegans and humans, revealing an evolutionarily conserved mechanism for cell fate protection. |
| Keywords: | Cell Fate Maintenance, Cell Fate Safeguarding, Reprogramming, Chromatin Remodeler, Facilitates Chromatin Transcription, FACT, Human Fibroblasts, Animals, Caenorhabditis elegans |
| Source: | Developmental Cell |
| ISSN: | 1534-5807 |
| Publisher: | Cell Press |
| Volume: | 46 |
| Number: | 5 |
| Page Range: | 611-626 |
| Date: | 10 September 2018 |
| Official Publication: | https://doi.org/10.1016/j.devcel.2018.07.006 |
| PubMed: | View item in PubMed |
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