Evidence map›Paper›PMID 16683039›Full record

ArticlePLoS genetics2006

DNA methylation supports intrinsic epigenetic memory in mammalian cells.

Yong-Qing Feng, Romain Desprat, Haiqing Fu, Emmanuel Olivier, Chii Mei Lin, Amanda Lobell, Shilpa N Gowda, Mirit I Aladjem, Eric E Bouhassira

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Review
  3. Regulation of Replication Origins.Advances in experimental medicine and biology · 2017
    Review
  4. Article
  5. The potential role of DNA methylation in abdominal aortic aneurysms.International journal of molecular sciences · 2015
    Article
  6. Review
  7. DNA modifications in the mammalian brain.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2014
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Epigenetic alterations in muscular disorders.Comparative and functional genomics · 2012
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

9 authors at 2 institutions in 1 country.

Yong-Qing FengDepartment of Medicine, Division of Hematology, Albert Einstein College Of Medicine, Bronx, New York, New York, United States of America.
Romain Desprat
Haiqing Fu
Emmanuel Olivier
Chii Mei Lin
Amanda Lobell
Shilpa N Gowda
Mirit I Aladjem
Eric E Bouhassira
Albert Einstein College of Medicine · USNational Cancer Institute · US

Funding

STEM CELLS AND GENE THERAPY MODELSP01HL055435 · NHLBI · YESHIVA UNIVERSITY · PI NAGEL, RONALD L · 1995 to 2004
$11.0M
Establishment and maintenance of repressed chromatinR01DK056845 · NIDDK · YESHIVA UNIVERSITY · PI BOUHASSIRA, ERIC E · 2000 to 2008
$2.8M
INITIATION OF DNA REPLICATION IN MAMMALIAN CELLSZ01BC010411 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ALADJEM, MIRIT · 2000 to 2008
$1.8M
A High-Throughput Transgenic Mouse Production SystemR21DK061799 · NIDDK · YESHIVA UNIVERSITY · PI BOUHASSIRA, ERIC E · 2001 to 2003
$501k
Intramural NIH HHSNHLBI NIH HHS HL55435NHLBI NIH HHS P01 HL055435NIDDK NIH HHS DK061799NIDDK NIH HHS DK56845NIDDK NIH HHS R01 DK056845
6 · The paper itself

Abstract

We have investigated the role of DNA methylation in the initiation and maintenance of silenced chromatin in somatic mammalian cells. We found that a mutated transgene, in which all the CpG dinucleotides have been eliminated, underwent transcriptional silencing to the same extent as the unmodified transgene. These observations demonstrate that DNA methylation is not required for silencing. The silenced CpG-free transgene exhibited all the features of heterochromatin, including silencing of transcriptional activity, delayed DNA replication, lack of histone H3 and H4 acetylation, lack of H3-K4 methylation, and enrichment in tri-methyl-H3-K9. In contrast, when we tested for transgene reactivation using a Cre recombinase-mediated inversion assay, we observed a marked difference between a CpG-free and an unmodified transgene: the CpG-free transgene resumed transcription and did not exhibit markers of heterochromatin whereas the unmodified transgene remained silenced. These data indicate that methylation of CpG residues conferred epigenetic memory in this system. These results also suggest that replication delay, lack of histone H3 and H4 acetylation, H3-K4 methylation, and enrichment in tri-methyl-H3-K9 are not sufficient to confer epigenetic memory. We propose that DNA methylation within transgenes serves as an intrinsic epigenetic memory to permanently silence transgenes and prevent their reactivation.

Indexed as

DNA MethylationEpigenesis, GeneticGene SilencingAnimalsGenetic MarkersGlobinsGreen Fluorescent ProteinsHistonesMammalsMethylationMiceMice, TransgenicRecombination, GeneticGenetic MarkersGlobinsGreen Fluorescent ProteinsHistones

Identifiers

PMID16683039
PMCPMC1449906
OpenAlexW2097459238

What OpenQuestion holds

Textmetadata
LicenceCC0
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.