dc.date.accessioned | 2023-12-12T17:33:51Z | |
dc.date.available | 2023-12-12T17:33:51Z | |
dc.date.created | 2023-11-29T14:35:09Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Fracassi, C Ugge', M Abdelhalim, Mohamed Ibrahim Mohamed Zapparoli, E Simoni, M Magliulo, D Mazza, D Lazarevic, D Morelli, MJ Collas, Philippe Bernardi, R . PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer. Nucleic Acids Research (NAR). 2023, 51(20)-11024 | |
dc.identifier.uri | http://hdl.handle.net/10852/106297 | |
dc.description.abstract | 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. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer | |
dc.title.alternative | ENEngelskEnglishPML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer | |
dc.type | Journal article | |
dc.creator.author | Fracassi, C | |
dc.creator.author | Ugge', M | |
dc.creator.author | Abdelhalim, Mohamed Ibrahim Mohamed | |
dc.creator.author | Zapparoli, E | |
dc.creator.author | Simoni, M | |
dc.creator.author | Magliulo, D | |
dc.creator.author | Mazza, D | |
dc.creator.author | Lazarevic, D | |
dc.creator.author | Morelli, MJ | |
dc.creator.author | Collas, Philippe | |
dc.creator.author | Bernardi, R | |
cristin.unitcode | 185,51,12,10 | |
cristin.unitname | Seksjon for Biokjemi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2205395 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nucleic Acids Research (NAR)&rft.volume=51&rft.spage=&rft.date=2023 | |
dc.identifier.jtitle | Nucleic Acids Research (NAR) | |
dc.identifier.volume | 51 | |
dc.identifier.issue | 20 | |
dc.identifier.startpage | 11024 | |
dc.identifier.endpage | 11039 | |
dc.identifier.doi | https://doi.org/10.1093/nar/gkad819 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0305-1048 | |
dc.type.version | PublishedVersion | |