Cargando…

Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C

Epstein–Barr virus proteins EBNA3A, EBNA3B and EBNA3C control hundreds of host genes after infection. Changes in epigenetic marks around EBNA3-regulated genes suggest that they exert transcriptional control in collaboration with epigenetic factors. The roles of polycomb repressive complex (PRC)2 sub...

Descripción completa

Detalles Bibliográficos
Autores principales: Paschos, Kostas, Bazot, Quentin, Lees, Jonathan, Farrell, Paul J, Allday, Martin J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451101/
https://www.ncbi.nlm.nih.gov/pubmed/30649516
http://dx.doi.org/10.1093/nar/gky1323
_version_ 1783409127222935552
author Paschos, Kostas
Bazot, Quentin
Lees, Jonathan
Farrell, Paul J
Allday, Martin J
author_facet Paschos, Kostas
Bazot, Quentin
Lees, Jonathan
Farrell, Paul J
Allday, Martin J
author_sort Paschos, Kostas
collection PubMed
description Epstein–Barr virus proteins EBNA3A, EBNA3B and EBNA3C control hundreds of host genes after infection. Changes in epigenetic marks around EBNA3-regulated genes suggest that they exert transcriptional control in collaboration with epigenetic factors. The roles of polycomb repressive complex (PRC)2 subunit SUZ12 and of PRC1 subunit BMI1 were assessed for their importance in EBNA3-mediated repression and activation. ChIP-seq experiments for SUZ12 and BMI1 were performed to determine their global localization on chromatin and analysis offered further insight into polycomb protein distribution in differentiated cells. Their localization was compared to that of each EBNA3 to resolve longstanding questions about the EBNA3–polycomb relationship. SUZ12 did not co-localize with any EBNA3, whereas EBNA3C co-localized significantly and co-immunoprecipitated with BMI1. In cells expressing a conditional EBNA3C, BMI1 was sequestered to EBNA3C-binding sites after EBNA3C activation. When SUZ12 or BMI1 was knocked down in the same cells, SUZ12 did not contribute to EBNA3C-mediated regulation. Surprisingly, after BMI1 knockdown, EBNA3C repressed equally efficiently but host gene activation by EBNA3C was impaired. This overturns previous assumptions about BMI1/PRC1 functions during EBNA3C-mediated regulation, for the first time identifies directly a host factor involved in EBNA3-mediated activation and provides a new insight into how PRC1 can be involved in gene activation.
format Online
Article
Text
id pubmed-6451101
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-64511012019-04-09 Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C Paschos, Kostas Bazot, Quentin Lees, Jonathan Farrell, Paul J Allday, Martin J Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Epstein–Barr virus proteins EBNA3A, EBNA3B and EBNA3C control hundreds of host genes after infection. Changes in epigenetic marks around EBNA3-regulated genes suggest that they exert transcriptional control in collaboration with epigenetic factors. The roles of polycomb repressive complex (PRC)2 subunit SUZ12 and of PRC1 subunit BMI1 were assessed for their importance in EBNA3-mediated repression and activation. ChIP-seq experiments for SUZ12 and BMI1 were performed to determine their global localization on chromatin and analysis offered further insight into polycomb protein distribution in differentiated cells. Their localization was compared to that of each EBNA3 to resolve longstanding questions about the EBNA3–polycomb relationship. SUZ12 did not co-localize with any EBNA3, whereas EBNA3C co-localized significantly and co-immunoprecipitated with BMI1. In cells expressing a conditional EBNA3C, BMI1 was sequestered to EBNA3C-binding sites after EBNA3C activation. When SUZ12 or BMI1 was knocked down in the same cells, SUZ12 did not contribute to EBNA3C-mediated regulation. Surprisingly, after BMI1 knockdown, EBNA3C repressed equally efficiently but host gene activation by EBNA3C was impaired. This overturns previous assumptions about BMI1/PRC1 functions during EBNA3C-mediated regulation, for the first time identifies directly a host factor involved in EBNA3-mediated activation and provides a new insight into how PRC1 can be involved in gene activation. Oxford University Press 2019-04-08 2019-01-15 /pmc/articles/PMC6451101/ /pubmed/30649516 http://dx.doi.org/10.1093/nar/gky1323 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Paschos, Kostas
Bazot, Quentin
Lees, Jonathan
Farrell, Paul J
Allday, Martin J
Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C
title Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C
title_full Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C
title_fullStr Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C
title_full_unstemmed Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C
title_short Requirement for PRC1 subunit BMI1 in host gene activation by Epstein–Barr virus protein EBNA3C
title_sort requirement for prc1 subunit bmi1 in host gene activation by epstein–barr virus protein ebna3c
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451101/
https://www.ncbi.nlm.nih.gov/pubmed/30649516
http://dx.doi.org/10.1093/nar/gky1323
work_keys_str_mv AT paschoskostas requirementforprc1subunitbmi1inhostgeneactivationbyepsteinbarrvirusproteinebna3c
AT bazotquentin requirementforprc1subunitbmi1inhostgeneactivationbyepsteinbarrvirusproteinebna3c
AT leesjonathan requirementforprc1subunitbmi1inhostgeneactivationbyepsteinbarrvirusproteinebna3c
AT farrellpaulj requirementforprc1subunitbmi1inhostgeneactivationbyepsteinbarrvirusproteinebna3c
AT alldaymartinj requirementforprc1subunitbmi1inhostgeneactivationbyepsteinbarrvirusproteinebna3c