Evidence map›Paper›PMID 25296254›Full record

ArticleNature2014

R-loops induce repressive chromatin marks over mammalian gene terminators.

Konstantina Skourti-Stathaki, Kinga Kamieniarz-Gdula, Nicholas J Proudfoot

Open access · greenAbstract read
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 263 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
263citing papers in PubMed, 1 pooled it
14.4field-weighted citation impact, top 1% 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

263 citing papers in PubMed, 1 synthesis or guideline pooled it, 384 citations in OpenAlex.

  1. Pooled it
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203 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Konstantina Skourti-StathakiSir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford OX1 3RE, UK.
Kinga Kamieniarz-GdulaSir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford OX1 3RE, UK.
Nicholas J ProudfootSir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford OX1 3RE, UK.
University of Oxford · GB

Funding

European Research Council 339270Wellcome Trust 091805Wellcome Trust 091805/Z/10/ZWellcome Trust 091911
6 · The paper itself

Abstract

The formation of R-loops is a natural consequence of the transcription process, caused by invasion of the DNA duplex by nascent transcripts. These structures have been considered rare transcriptional by-products with potentially harmful effects on genome integrity owing to the fragility of the displaced DNA coding strand. However, R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes. Furthermore, we have previously shown that R-loops are particularly enriched over G-rich terminator elements. These facilitate RNA polymerase II (Pol II) pausing before efficient termination. Here we reveal an unanticipated link between R-loops and RNA-interference-dependent H3K9me2 formation over pause-site termination regions in mammalian protein-coding genes. We show that R-loops induce antisense transcription over these pause elements, which in turn leads to the generation of double-stranded RNA and the recruitment of DICER, AGO1, AGO2 and the G9a histone lysine methyltransferase. Consequently, an H3K9me2 repressive mark is formed and heterochromatin protein 1γ (HP1γ) is recruited, which reinforces Pol II pausing before efficient transcriptional termination. We predict that R-loops promote a chromatin architecture that defines the termination region for a substantial subset of mammalian genes.

Indexed as

Gene Expression RegulationActinsAnimalsArgonaute ProteinsCell LineChromatinHeLa CellsHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHistonesHumansMiceRNA InterferenceRNA Polymerase IITerminator Regions, GeneticActinsAGO2 protein, humanArgonaute ProteinsChromatinEHMT2 protein, humanHistocompatibility AntigensHistone-Lysine N-MethyltransferaseHistonesRNA Polymerase II

Identifiers

PMID25296254
PMCPMC4272244
OpenAlexW1989540449

What OpenQuestion holds

Textmetadata
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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.