RRC ID 56186
Author 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.
Title FACT Sets a Barrier for Cell Fate Reprogramming in Caenorhabditis elegans and Human Cells.
Journal Dev Cell
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.
Volume 46(5)
Pages 611-626.e12
Published 2018-9-10
DOI 10.1016/j.devcel.2018.07.006
PII S1534-5807(18)30559-8
PMID 30078731
PMC PMC6137076
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Differentiation Cell Lineage Cells, Cultured Cellular Reprogramming* Chromatin / genetics Chromatin / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Fibroblasts / cytology Fibroblasts / metabolism Gene Expression Regulation* High Mobility Group Proteins / genetics High Mobility Group Proteins / metabolism* Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / physiology* Transcriptional Elongation Factors / genetics Transcriptional Elongation Factors / metabolism* Transcriptome
IF 9.19
Times Cited 15
C.elegans tm1873 tm2539