Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109239
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Léveillé, Nicolas | - |
dc.contributor.author | Melo, Carlos A. | - |
dc.contributor.author | Rooijers, Koos | - |
dc.contributor.author | Díaz-Lagares, Angel | - |
dc.contributor.author | Melo, Sonia A. | - |
dc.contributor.author | Korkmaz, Gozde | - |
dc.contributor.author | Lopes, Rui | - |
dc.contributor.author | Moqadam, Farhad Akbari | - |
dc.contributor.author | Maia, Ana R | - |
dc.contributor.author | Wijchers, Patrick J. | - |
dc.contributor.author | Geeven, Geert | - |
dc.contributor.author | den Boer, Monique L. | - |
dc.contributor.author | Kalluri, Raghu | - |
dc.contributor.author | de Laat, Wouter | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Agami, Reuven | - |
dc.date.accessioned | 2023-10-04T11:04:30Z | - |
dc.date.available | 2023-10-04T11:04:30Z | - |
dc.date.issued | 2015-03-27 | - |
dc.identifier.issn | 2041-1723 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/109239 | - |
dc.description.abstract | p53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs (lncRNAs) are prominent regulators of chromatin dynamics, we hypothesized that p53-induced lncRNAs contribute to the activation of enhancers by p53. Among p53-induced lncRNAs, we identified LED and demonstrate that its suppression attenuates p53 function. Chromatin-binding and eRNA expression analyses show that LED associates with and activates strong enhancers. One prominent target of LED was located at an enhancer region within CDKN1A gene, a potent p53-responsive cell cycle inhibitor. LED knockdown reduces CDKN1A enhancer induction and activity, and cell cycle arrest following p53 activation. Finally, promoter-associated hypermethylation analysis shows silencing of LED in human tumours. Thus, our study identifies a new layer of complexity in the p53 pathway and suggests its dysregulation in cancer. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | SFRH/BD/33472/2008 | pt |
dc.relation | SFRH/BD/74476/2010; POPH/FSE) | pt |
dc.relation | Human Frontiers Program to S.A.M | pt |
dc.relation | Netherlands Organization for Scientific Research (‘NWO’ Vidi grant) to M.L.dB. | pt |
dc.relation | F.A.M., ‘Sara Borrell’ postdoctoral contract (CD12/00738) from the ISCIII at the Spanish Ministry of Economy and Competitiveness to A.D.L., European Research Council (ERC) Advanced Grant EPINORC (# 268626) to M.E. | pt |
dc.relation | European Research Council (ERC) Advanced Grant EnhReg to R.A. | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Adenocarcinoma | pt |
dc.subject.mesh | Breast Neoplasms | pt |
dc.subject.mesh | Chromatin Immunoprecipitation | pt |
dc.subject.mesh | Cyclin-Dependent Kinase Inhibitor p21 | pt |
dc.subject.mesh | DNA Methylation | pt |
dc.subject.mesh | Enhancer Elements, Genetic | pt |
dc.subject.mesh | Female | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | In Situ Hybridization, Fluorescence | pt |
dc.subject.mesh | MCF-7 Cells | pt |
dc.subject.mesh | Promoter Regions, Genetic | pt |
dc.subject.mesh | RNA, Long Noncoding | pt |
dc.subject.mesh | Real-Time Polymerase Chain Reaction | pt |
dc.subject.mesh | Sequence Analysis, RNA | pt |
dc.subject.mesh | Tumor Suppressor Protein p53 | pt |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | pt |
dc.title | Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA | pt |
dc.type | article | - |
degois.publication.firstPage | 6520 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Nature Communications | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1038/ncomms7520 | pt |
degois.publication.volume | 6 | pt |
dc.date.embargo | 2015-03-27 | * |
uc.date.periodoEmbargo | 0 | pt |
item.openairetype | article | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-2190-547X | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Genomewide-profiling-of-p53regulated-enhancer-RNAs-uncovers-a-subset-of-enhancers-controlled-by-a-lncRNANature-Communications.pdf | 1.54 MB | Adobe PDF | View/Open |
Page view(s)
24
checked on Jul 17, 2024
Download(s)
15
checked on Jul 17, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License