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BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract
The tumor suppressor BRCA1 is considered a master regulator of genome integrity. Although widely recognized for its DNA repair functions, BRCA1 has also been implicated in various mechanisms of chromatin remodeling and transcription regulation. However, the precise role that BRCA1 plays in these pro...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034626/ https://www.ncbi.nlm.nih.gov/pubmed/33660782 http://dx.doi.org/10.1093/nar/gkab111 |
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author | Barrows, John K Fullbright, George Long, David T |
author_facet | Barrows, John K Fullbright, George Long, David T |
author_sort | Barrows, John K |
collection | PubMed |
description | The tumor suppressor BRCA1 is considered a master regulator of genome integrity. Although widely recognized for its DNA repair functions, BRCA1 has also been implicated in various mechanisms of chromatin remodeling and transcription regulation. However, the precise role that BRCA1 plays in these processes has been difficult to establish due to the widespread consequences of its cellular dysfunction. Here, we use nucleoplasmic extract derived from the eggs of Xenopus laevis to investigate the role of BRCA1 in a cell-free transcription system. We report that BRCA1-BARD1 suppresses transcription initiation independent of DNA damage signaling and its established role in histone H2A ubiquitination. BRCA1-BARD1 acts through a histone intermediate, altering acetylation of histone H4K8 and recruitment of the chromatin reader and oncogene regulator BRD4. Together, these results establish a functional relationship between an established (BRCA1) and emerging (BRD4) regulator of genome integrity. |
format | Online Article Text |
id | pubmed-8034626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80346262021-04-14 BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract Barrows, John K Fullbright, George Long, David T Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The tumor suppressor BRCA1 is considered a master regulator of genome integrity. Although widely recognized for its DNA repair functions, BRCA1 has also been implicated in various mechanisms of chromatin remodeling and transcription regulation. However, the precise role that BRCA1 plays in these processes has been difficult to establish due to the widespread consequences of its cellular dysfunction. Here, we use nucleoplasmic extract derived from the eggs of Xenopus laevis to investigate the role of BRCA1 in a cell-free transcription system. We report that BRCA1-BARD1 suppresses transcription initiation independent of DNA damage signaling and its established role in histone H2A ubiquitination. BRCA1-BARD1 acts through a histone intermediate, altering acetylation of histone H4K8 and recruitment of the chromatin reader and oncogene regulator BRD4. Together, these results establish a functional relationship between an established (BRCA1) and emerging (BRD4) regulator of genome integrity. Oxford University Press 2021-02-28 /pmc/articles/PMC8034626/ /pubmed/33660782 http://dx.doi.org/10.1093/nar/gkab111 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Barrows, John K Fullbright, George Long, David T BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract |
title | BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract |
title_full | BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract |
title_fullStr | BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract |
title_full_unstemmed | BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract |
title_short | BRCA1-BARD1 regulates transcription through BRD4 in Xenopus nucleoplasmic extract |
title_sort | brca1-bard1 regulates transcription through brd4 in xenopus nucleoplasmic extract |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034626/ https://www.ncbi.nlm.nih.gov/pubmed/33660782 http://dx.doi.org/10.1093/nar/gkab111 |
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