RESUMEN

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.

Asunto(s)

Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Reprogramación Celular , Cromatina/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Proteínas del Grupo de Alta Movilidad/metabolismo , Células Madre Pluripotentes Inducidas/fisiología , Factores de Elongación Transcripcional/metabolismo , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/crecimiento & desarrollo , Proteínas de Caenorhabditis elegans/genética , Diferenciación Celular , Linaje de la Célula , Células Cultivadas , Cromatina/genética , Proteínas de Unión al ADN/genética , Fibroblastos/citología , Fibroblastos/metabolismo , Proteínas del Grupo de Alta Movilidad/genética , Humanos , Células Madre Pluripotentes Inducidas/citología , Factores de Elongación Transcripcional/genética , Transcriptoma