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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2018
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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. |
format | Online Article Text |
id | pubmed-6238418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
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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