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| Item Type: | Article |
|---|---|
| Title: | FACT sets a barrier for cell fate reprogramming in Caenorhabditis elegans and human cells |
| Creators Name: | Kolundzic, E., Ofenbauer, A., Bulut, S.I., Uyar, B., Baytek, G., Sommermeier, A., Seelk, S., He, M., Hirsekorn, A., Vucicevic, D., Akalin, A., Diecke, S., Lacadie, S.A. and Tursun, B. |
| 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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