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

Bibliographic Details
Main Author: Sabino, João C.
Publication Date: 2022
Other Authors: 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
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10362/134768
Summary: 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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network_name_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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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:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T18:00:17Zoai:run.unl.pt:10362/134768Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:31:33.904788Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
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:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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