Logo do repositório
 
Publicação

Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops

2022-02Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorSabino, João C.
dc.contributor.authorde Almeida, Madalena R.
dc.contributor.authorAbreu, Patrícia Lona
dc.contributor.authorFerreira, Ana M.
dc.contributor.authorCaldas, Paulo
dc.contributor.authorDomingues, Marco M.
dc.contributor.authorSantos, Nuno C.
dc.contributor.authorAzzalin, Claus M.
dc.contributor.authorGrosso, Ana Rita
dc.contributor.authorde Almeida, Sérgio Fernandes
dc.contributor.institutionUCIBIO - Applied Molecular Biosciences Unit
dc.contributor.institutionDCV - Departamento de Ciências da Vida
dc.contributor.pbleLife Sciences Publications
dc.date.accessioned2022-03-17T23:23:22Z
dc.date.available2022-03-17T23:23:22Z
dc.date.issued2022-02
dc.descriptionPTDC/BIA-MOL/30438/2017 PTDC/MED-OUT/4301/2020 RiboMed 857119 PD/BD/128292/2017 LCF/PR/HP21/52310016 PTDC/BIA-MOL/6624/2020 PTDC/MED-ONC/7864/2020
dc.description.abstractDNA oxidation by ten-eleven translocation (TET) family enzymes is essential for epigenetic reprogramming. The conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) initiates developmental and cell-type-specific transcriptional programs through mechanisms that include changes in the chromatin structure. Here, we show that the presence of 5hmC in the transcribed gene promotes the annealing of the nascent RNA to the template DNA strand, leading to the formation of an R-loop. Depletion of TET enzymes reduced global R-loops in the absence of gene expression changes, whereas CRISPR-mediated tethering of TET to an active gene promoted the formation of R-loops. The genome-wide distribution of 5hmC and R-loops shows a positive correlation in mouse and human stem cells and overlap in half of all active genes. Moreover, R-loop resolution leads to differential expression of a subset of genes that are involved in crucial events during stem cell proliferation. Altogether, our data reveal that epigenetic reprogramming via TET activity promotes co-transcriptional R-loop formation, disclosing new mechanisms of gene expression regulation.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2689309
dc.identifier.doi10.7554/ELIFE.69476
dc.identifier.issn2050-084X
dc.identifier.otherPURE: 42333114
dc.identifier.otherPURE UUID: 584d00c5-5cc9-4f40-b31f-cc9630c33c0d
dc.identifier.otherScopus: 85125583328
dc.identifier.otherPubMed: 35191837
dc.identifier.otherPubMedCentral: PMC8896830
dc.identifier.otherORCID: /0000-0001-6974-4209/work/110049594
dc.identifier.otherWOS: 000766965300001
dc.identifier.urihttp://hdl.handle.net/10362/134768
dc.identifier.urlhttps://www.scopus.com/pages/publications/85125583328
dc.language.isoeng
dc.peerreviewedyes
dc.subjectGeneral Neuroscience
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Immunology and Microbiology
dc.titleEpigenetic reprogramming by TET enzymes impacts co-transcriptional R-loopsen
dc.typejournal article
degois.publication.titleeLife
degois.publication.volume11
dspace.entity.typePublication
rcaap.rightsopenAccess

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
elife_69476_v2.pdf
Tamanho:
2.56 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

FCT: DCV - Artigos em revista internacional com arbitragem científica