Evidence map›Paper›PMID 35191837›Full record

ArticleeLife2022

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

João C Sabino, Madalena R de Almeida, Patrícia L Abreu, Ana M Ferreira, Paulo Caldas, Marco M Domingues, Nuno C Santos, Claus M Azzalin, Ana Rita Grosso, Sérgio Fernandes de Almeida

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
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  16. DNA Glycosylases Define the Outcome of Endogenous Base Modifications.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

João C SabinoInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.ORCID 0000-0001-7991-4291
Madalena R de AlmeidaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.ORCID 0000-0001-9539-3289
Patrícia L AbreuInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.ORCID 0000-0002-6387-8537
Ana M FerreiraInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Paulo CaldasAssociate laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade Nova de Lisboa, Caparica, Portugal.
Marco M DominguesInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Nuno C SantosInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Claus M AzzalinInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.ORCID 0000-0002-9396-1980
Ana Rita GrossoAssociate laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade Nova de Lisboa, Caparica, Portugal.ORCID 0000-0001-6974-4209
Sérgio Fernandes de AlmeidaInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.ORCID 0000-0002-7774-1355
University of Lisbon · PTRede de Química e Tecnologia · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA 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.

Indexed as

DioxygenasesR-Loop Structures5-MethylcytosineAnimalsCytosineDNADNA MethylationEpigenesis, GeneticEpigenomicsHumansMice5-MethylcytosineCytosineDioxygenasesDNAchromosomesDNA hydroxymethylationgene expressionhumanmouseR-loopsstem cellsTET enzymes

Identifiers

PMID35191837
PMCPMC8896830
OpenAlexW4221036932

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.