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Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells

The conserved and essential histone chaperone, facilitates chromatin transcription (FACT), reorganizes nucleosomes during DNA transcription, replication, and repair and ensures both efficient elongation of RNA Pol II and nucleosome integrity. In mammalian cells, FACT is a heterodimer, consisting of...

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Autores principales: Mylonas, Constantine, Tessarz, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238418/
https://www.ncbi.nlm.nih.gov/pubmed/30456357
http://dx.doi.org/10.26508/lsa.201800085
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author Mylonas, Constantine
Tessarz, Peter
author_facet Mylonas, Constantine
Tessarz, Peter
author_sort Mylonas, Constantine
collection PubMed
description The conserved and essential histone chaperone, facilitates chromatin transcription (FACT), reorganizes nucleosomes during DNA transcription, replication, and repair and ensures both efficient elongation of RNA Pol II and nucleosome integrity. In mammalian cells, FACT is a heterodimer, consisting of SSRP1 and SUPT16. Here, we show that in contrast to yeast, FACT accumulates at the transcription start site of genes reminiscent of RNA polymerase II profile. Depletion of FACT in mouse embryonic stem cells leads to deregulation of developmental and pro-proliferative genes concomitant with hyper-proliferation of mES cells. Using MNase-seq, Assay for Transposase-Accessible Chromatin sequencing, and nascent elongating transcript sequencing, we show that up-regulation of genes coincides with loss of nucleosomes upstream of the transcription start site and concomitant increase in antisense transcription, indicating that FACT impacts the promoter architecture to regulate the expression of these genes. Finally, we demonstrate a role for FACT in cell fate determination and show that FACT depletion primes embryonic stem cells for the neuronal lineage.
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spelling pubmed-62384182018-11-19 Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells Mylonas, Constantine Tessarz, Peter Life Sci Alliance Research Articles The conserved and essential histone chaperone, facilitates chromatin transcription (FACT), reorganizes nucleosomes during DNA transcription, replication, and repair and ensures both efficient elongation of RNA Pol II and nucleosome integrity. In mammalian cells, FACT is a heterodimer, consisting of SSRP1 and SUPT16. Here, we show that in contrast to yeast, FACT accumulates at the transcription start site of genes reminiscent of RNA polymerase II profile. Depletion of FACT in mouse embryonic stem cells leads to deregulation of developmental and pro-proliferative genes concomitant with hyper-proliferation of mES cells. Using MNase-seq, Assay for Transposase-Accessible Chromatin sequencing, and nascent elongating transcript sequencing, we show that up-regulation of genes coincides with loss of nucleosomes upstream of the transcription start site and concomitant increase in antisense transcription, indicating that FACT impacts the promoter architecture to regulate the expression of these genes. Finally, we demonstrate a role for FACT in cell fate determination and show that FACT depletion primes embryonic stem cells for the neuronal lineage. Life Science Alliance LLC 2018-06-13 /pmc/articles/PMC6238418/ /pubmed/30456357 http://dx.doi.org/10.26508/lsa.201800085 Text en © 2018 Tessarz and Mylonas https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Mylonas, Constantine
Tessarz, Peter
Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
title Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
title_full Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
title_fullStr Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
title_full_unstemmed Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
title_short Transcriptional repression by FACT is linked to regulation of chromatin accessibility at the promoter of ES cells
title_sort transcriptional repression by fact is linked to regulation of chromatin accessibility at the promoter of es cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238418/
https://www.ncbi.nlm.nih.gov/pubmed/30456357
http://dx.doi.org/10.26508/lsa.201800085
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