Evidence map›Paper›PMID 21427230›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing.

Danny C Leung, Kevin B Dong, Irina A Maksakova, Preeti Goyal, Ruth Appanah, Sandra Lee, Makoto Tachibana, Yoichi Shinkai, Bernhard Lehnertz, Dixie L Mager and 2 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

74 citing papers in PubMed, 123 citations in OpenAlex.

  1. Repurposing antifolates as G9a methyltransferase inhibitors for potential Alzheimer's disease therapeutics via 3D QSAR/pharmacophore mapping and experimental validations.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
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14 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

12 authors at 3 institutions in 2 countries.

Danny C LeungDepartment of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Kevin B Dong
Irina A Maksakova
Preeti Goyal
Ruth Appanah
Sandra Lee
Makoto Tachibana
Yoichi Shinkai
Bernhard Lehnertz
Dixie L Mager
Fabio Rossi
Matthew C Lorincz
University of British Columbia · CABC Cancer Agency · CAKyoto University · JP

Funding

Canadian Institutes of Health Research 77805Canadian Institutes of Health Research 92090
6 · The paper itself

Abstract

Methylation on lysine 9 of histone H3 (H3K9me) and DNA methylation play important roles in the transcriptional silencing of specific genes and repetitive elements. Both marks are detected on class I and II endogenous retroviruses (ERVs) in murine embryonic stem cells (mESCs). Recently, we reported that the H3K9-specific lysine methyltransferase (KMTase) Eset/Setdb1/KMT1E is required for H3K9me3 and the maintenance of silencing of ERVs in mESCs. In contrast, G9a/Ehmt2/KMT1C is dispensable, despite the fact that this KMTase is required for H3K9 dimethylation (H3K9me2) and efficient DNA methylation of these retroelements. Transcription of the exogenous retrovirus (XRV) Moloney murine leukemia virus is rapidly extinguished after integration in mESCs, concomitant with de novo DNA methylation. However, the role that H3K9 KMTases play in this process has not been addressed. Here, we demonstrate that G9a, but not Suv39h1 or Suv39h2, is required for silencing of newly integrated Moloney murine leukemia virus-based vectors in mESCs. The silencing defect in G9a(-/-) cells is accompanied by a reduction of H3K9me2 at the proviral LTR, indicating that XRVs are direct targets of G9a. Furthermore, de novo DNA methylation of newly integrated proviruses is impaired in the G9a(-/-) line, phenocopying proviral DNA methylation and silencing defects observed in Dnmt3a-deficient mESCs. Once established, however, maintenance of silencing of XRVs, like ERVs, is dependent exclusively on the KMTase Eset. Taken together, these observations reveal that in mESCs, the H3K9 KMTase G9a is required for the establishment, but not for the maintenance, of silencing of newly integrated proviruses.

Indexed as

AnimalsBlotting, WesternChromatin ImmunoprecipitationDNA (Cytosine-5-)-MethyltransferasesDNA MethylationEmbryonic Stem CellsEndogenous RetrovirusesFlow CytometryGene SilencingGenetic VectorsHistone-Lysine N-MethyltransferaseMiceMice, KnockoutMoloney murine leukemia virusProvirusesReverse Transcriptase Polymerase Chain ReactionDNA (Cytosine-5-)-MethyltransferasesG9a protein, mouseHistone-Lysine N-Methyltransferase

Identifiers

PMID21427230
PMCPMC3078371
OpenAlexW2040527067

What OpenQuestion holds

Textmetadata
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.