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PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer
The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors localize to be regulated. In addition, associations of PML and PML-NBs with chromatin are described in various cell types, further implicating PML in transcri...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10639071/ https://www.ncbi.nlm.nih.gov/pubmed/37823593 http://dx.doi.org/10.1093/nar/gkad819 |
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author | Fracassi, Cristina Ugge', Martina Abdelhalim, Mohamed Zapparoli, Ettore Simoni, Matilde Magliulo, Daniela Mazza, Davide Lazarevic, Dejan Morelli, Marco J Collas, Philippe Bernardi, Rosa |
author_facet | Fracassi, Cristina Ugge', Martina Abdelhalim, Mohamed Zapparoli, Ettore Simoni, Matilde Magliulo, Daniela Mazza, Davide Lazarevic, Dejan Morelli, Marco J Collas, Philippe Bernardi, Rosa |
author_sort | Fracassi, Cristina |
collection | PubMed |
description | The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors localize to be regulated. In addition, associations of PML and PML-NBs with chromatin are described in various cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in cellular contexts where it promotes relevant phenotypes is still lacking. We examined PML chromatin association in triple-negative breast cancer (TNBC) cell lines, where it exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain discrete gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a relevant gene regulatory function. We also find that PML plays indirect regulatory roles in TNBC cells by promoting the expression of pro-metastatic genes outside PADs. Our findings suggest that PML is an important transcriptional regulator of pro-oncogenic metagenes in TNBC cells, via transcriptional regulation and epigenetic organization of heterochromatin domains that embed regions of local transcriptional activity. |
format | Online Article Text |
id | pubmed-10639071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-106390712023-11-15 PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer Fracassi, Cristina Ugge', Martina Abdelhalim, Mohamed Zapparoli, Ettore Simoni, Matilde Magliulo, Daniela Mazza, Davide Lazarevic, Dejan Morelli, Marco J Collas, Philippe Bernardi, Rosa Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors localize to be regulated. In addition, associations of PML and PML-NBs with chromatin are described in various cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in cellular contexts where it promotes relevant phenotypes is still lacking. We examined PML chromatin association in triple-negative breast cancer (TNBC) cell lines, where it exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain discrete gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a relevant gene regulatory function. We also find that PML plays indirect regulatory roles in TNBC cells by promoting the expression of pro-metastatic genes outside PADs. Our findings suggest that PML is an important transcriptional regulator of pro-oncogenic metagenes in TNBC cells, via transcriptional regulation and epigenetic organization of heterochromatin domains that embed regions of local transcriptional activity. Oxford University Press 2023-10-12 /pmc/articles/PMC10639071/ /pubmed/37823593 http://dx.doi.org/10.1093/nar/gkad819 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://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 Fracassi, Cristina Ugge', Martina Abdelhalim, Mohamed Zapparoli, Ettore Simoni, Matilde Magliulo, Daniela Mazza, Davide Lazarevic, Dejan Morelli, Marco J Collas, Philippe Bernardi, Rosa PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
title | PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
title_full | PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
title_fullStr | PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
title_full_unstemmed | PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
title_short | PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
title_sort | pml modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10639071/ https://www.ncbi.nlm.nih.gov/pubmed/37823593 http://dx.doi.org/10.1093/nar/gkad819 |
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