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FACT Sets a Barrier for Cell Fate Reprogramming in Caenorhabditis elegans and Human Cells.


Kolundzic E, Ofenbauer A, Bulut SI, Uyar B, Baytek G, Sommermeier A, Seelk S, He M, Hirsekorn A, Vucicevic D, Akalin A, Diecke S, Lacadie SA, Tursun B

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.

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Published
September, 2018

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