FACT sets a barrier for cell fate reprogramming in Caenorhabditis elegans and human cells


  • E. Kolundzic
  • A. Ofenbauer
  • S.I. Bulut
  • B. Uyar
  • G. Baytek
  • A. Sommermeier
  • S. Seelk
  • M. He
  • A. Hirsekorn
  • D. Vucicevic
  • A. Akalin
  • S. Diecke
  • S.A. Lacadie
  • B. Tursun


  • Developmental Cell


  • Dev Cell 46 (5): 611-626


  • 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.