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FACT sets a barrier for cell fate reprogramming in C. elegans and Human

Ena Kolundzic, Andreas Ofenbauer, Bora Uyar, Anne Sommermeier, Stefanie Seelk, Mei He, Gülkiz Baytek, Altuna Akalin, Sebastian Diecke, Scott A. Lacadie, Baris Tursun
doi: https://doi.org/10.1101/185116
Ena Kolundzic
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Andreas Ofenbauer
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Bora Uyar
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Anne Sommermeier
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
2Department of Biology, Humboldt University, Berlin, Germany
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Stefanie Seelk
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Mei He
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Gülkiz Baytek
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Altuna Akalin
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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Sebastian Diecke
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
3Berlin Institute of Health, Berlin, Germany
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  • For correspondence: Baris.Tursun@mdc-berlin.de scott.lacadie@mdc-berlin.de sebastian.diecke@mdc-berlin.de
Scott A. Lacadie
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
3Berlin Institute of Health, Berlin, Germany
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  • For correspondence: Baris.Tursun@mdc-berlin.de scott.lacadie@mdc-berlin.de sebastian.diecke@mdc-berlin.de
Baris Tursun
1Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
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  • For correspondence: Baris.Tursun@mdc-berlin.de scott.lacadie@mdc-berlin.de sebastian.diecke@mdc-berlin.de
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The chromatin regulator FACT (Facilitates Chromatin Transcription) is essential for ensuring stable gene expression by promoting transcription. In a genetic screen using C. 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 reprogramming barrier is conserved in humans as we show that FACT depletion enhances reprogramming of fibroblasts into stem cells and neurons. Such activity of FACT is unexpected since known reprogramming barriers typically repress gene expression by silencing chromatin. In contrast, FACT is a positive regulator of gene expression suggesting an unprecedented link of cell fate maintenance with counteracting alternative cell identities. This notion is supported by ATAC-seq analysis showing that FACT depletion results in decreased but also increased chromatin accessibility for transcription factors. 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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  • Lead Contact: Baris.Tursun{at}mdc-berlin.de (BT)

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 06, 2017.
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FACT sets a barrier for cell fate reprogramming in C. elegans and Human
Ena Kolundzic, Andreas Ofenbauer, Bora Uyar, Anne Sommermeier, Stefanie Seelk, Mei He, Gülkiz Baytek, Altuna Akalin, Sebastian Diecke, Scott A. Lacadie, Baris Tursun
bioRxiv 185116; doi: https://doi.org/10.1101/185116
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FACT sets a barrier for cell fate reprogramming in C. elegans and Human
Ena Kolundzic, Andreas Ofenbauer, Bora Uyar, Anne Sommermeier, Stefanie Seelk, Mei He, Gülkiz Baytek, Altuna Akalin, Sebastian Diecke, Scott A. Lacadie, Baris Tursun
bioRxiv 185116; doi: https://doi.org/10.1101/185116

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