Evidence map›Paper›PMID 22174693›Full record

ArticlePLoS genetics2011

Genomic distribution and inter-sample variation of non-CpG methylation across human cell types.

Michael J Ziller, Fabian Müller, Jing Liao, Yingying Zhang, Hongcang Gu, Christoph Bock, Patrick Boyle, Charles B Epstein, Bradley E Bernstein, Thomas Lengauer and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 236 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
236citing papers in PubMed, 2 pooled it
12.6field-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

236 citing papers in PubMed, 2 syntheses or guidelines pooled it, 402 citations in OpenAlex.

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  19. Basic Epigenetic Mechanisms.Sub-cellular biochemistry · 2025
    Review
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176 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

Michael J ZillerBroad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
Fabian Müller
Jing Liao
Yingying Zhang
Hongcang Gu
Christoph Bock
Patrick Boyle
Charles B Epstein
Bradley E Bernstein
Thomas Lengauer
Andreas Gnirke
Alexander Meissner
Broad Institute · USHarvard Stem Cell Institute · USHarvard University · USMax Planck Institute for Informatics · DECenter for Systems Biology · US

Funding

Production sequencing of reference human epigenomesU01ES017155 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERNSTEIN, BRADLEY EVAN, MEISSNER, ALEXANDER · 2008 to 2012
$15.4M
Howard Hughes Medical InstituteNIEHS NIH HHS U01 ES017155NIEHS NIH HHS U01ES017155
6 · The paper itself

Abstract

DNA methylation plays an important role in development and disease. The primary sites of DNA methylation in vertebrates are cytosines in the CpG dinucleotide context, which account for roughly three quarters of the total DNA methylation content in human and mouse cells. While the genomic distribution, inter-individual stability, and functional role of CpG methylation are reasonably well understood, little is known about DNA methylation targeting CpA, CpT, and CpC (non-CpG) dinucleotides. Here we report a comprehensive analysis of non-CpG methylation in 76 genome-scale DNA methylation maps across pluripotent and differentiated human cell types. We confirm non-CpG methylation to be predominantly present in pluripotent cell types and observe a decrease upon differentiation and near complete absence in various somatic cell types. Although no function has been assigned to it in pluripotency, our data highlight that non-CpG methylation patterns reappear upon iPS cell reprogramming. Intriguingly, the patterns are highly variable and show little conservation between different pluripotent cell lines. We find a strong correlation of non-CpG methylation and DNMT3 expression levels while showing statistical independence of non-CpG methylation from pluripotency associated gene expression. In line with these findings, we show that knockdown of DNMTA and DNMT3B in hESCs results in a global reduction of non-CpG methylation. Finally, non-CpG methylation appears to be spatially correlated with CpG methylation. In summary these results contribute further to our understanding of cytosine methylation patterns in human cells using a large representative sample set.

Indexed as

AnimalsCell DifferentiationCell LineCpG IslandsCytosineDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Methyltransferase 3BEmbryonic Stem CellsEpigenesis, GeneticGene ExpressionGene Knockdown TechniquesGenome, HumanHumansInduced Pluripotent Stem CellsCytosineDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BDNMT3A protein, humanRNA, Small Interfering

Identifiers

PMID22174693
PMCPMC3234221
OpenAlexW2130222411

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.