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

Detalhes bibliográficos
Autor(a) principal: Sabino, João C.
Data de Publicação: 2022
Outros Autores: de Almeida, Madalena R., Abreu, Patrícia Lona, Ferreira, Ana M., Caldas, Paulo, Domingues, Marco M., Santos, Nuno C., Azzalin, Claus M., Grosso, Ana Rita, de Almeida, Sérgio Fernandes
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/134768
Resumo: PTDC/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
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spelling Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loopsNeuroscience(all)Biochemistry, Genetics and Molecular Biology(all)Immunology and Microbiology(all)PTDC/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/7864/2020DNA 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.UCIBIO - Applied Molecular Biosciences UnitDCV - Departamento de Ciências da VidaRUNSabino, João C.de Almeida, Madalena R.Abreu, Patrícia LonaFerreira, Ana M.Caldas, PauloDomingues, Marco M.Santos, Nuno C.Azzalin, Claus M.Grosso, Ana Ritade Almeida, Sérgio Fernandes2022-03-17T23:23:22Z2022-022022-02-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/134768eng2050-084XPURE: 42333114https://doi.org/10.7554/ELIFE.69476info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-22T18:00:17Zoai:run.unl.pt:10362/134768Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:00:17Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
title Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
spellingShingle Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
Sabino, João C.
Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)
title_short Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
title_full Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
title_fullStr Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
title_full_unstemmed Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
title_sort Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops
author Sabino, João C.
author_facet Sabino, João C.
de Almeida, Madalena R.
Abreu, Patrícia Lona
Ferreira, Ana M.
Caldas, Paulo
Domingues, Marco M.
Santos, Nuno C.
Azzalin, Claus M.
Grosso, Ana Rita
de Almeida, Sérgio Fernandes
author_role author
author2 de Almeida, Madalena R.
Abreu, Patrícia Lona
Ferreira, Ana M.
Caldas, Paulo
Domingues, Marco M.
Santos, Nuno C.
Azzalin, Claus M.
Grosso, Ana Rita
de Almeida, Sérgio Fernandes
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv UCIBIO - Applied Molecular Biosciences Unit
DCV - Departamento de Ciências da Vida
RUN
dc.contributor.author.fl_str_mv Sabino, João C.
de Almeida, Madalena R.
Abreu, Patrícia Lona
Ferreira, Ana M.
Caldas, Paulo
Domingues, Marco M.
Santos, Nuno C.
Azzalin, Claus M.
Grosso, Ana Rita
de Almeida, Sérgio Fernandes
dc.subject.por.fl_str_mv Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)
topic Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Immunology and Microbiology(all)
description PTDC/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
publishDate 2022
dc.date.none.fl_str_mv 2022-03-17T23:23:22Z
2022-02
2022-02-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/134768
url http://hdl.handle.net/10362/134768
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2050-084X
PURE: 42333114
https://doi.org/10.7554/ELIFE.69476
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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