期刊
DEVELOPMENTAL CELL
卷 46, 期 5, 页码 611-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2018.07.006
关键词
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资金
- NIH
- Stiftung Charite
- ERC [CIG PCIG12-GA-2012-333922]
- Max Delbrueck Center for Molecular Medicine in the Helmholtz Association
- [ERC-StG-2014-637530]
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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