Evidence map›Paper›PMID 24057217›Full record

ArticleNucleic acids research2014

Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites.

Alexey Kozlenkov, Panos Roussos, Alisa Timashpolsky, Mihaela Barbu, Sergei Rudchenko, Marina Bibikova, Brandy Klotzle, William Byne, Rebecca Lyddon, Antonio Fabio Di Narzo and 3 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
–field-weighted citation impact
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

99 citing papers in PubMed.

  1. Review
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  11. Article
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  14. Article
  15. DNA Methylation Profiles ofInternational journal of molecular sciences · 2022
    Article
  16. Review
  17. Article
  18. Article
  19. Epigenetics of neural differentiation: Spotlight on enhancers.Frontiers in cell and developmental biology · 2022
    Review
  20. Article

39 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

13 authors.

Alexey KozlenkovVISN 3 Mental Illness Research, Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, NY, USA, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA, Research Division, Hospital for Special Surgery, New York, NY, USA, Illumina, Inc., San Diego, CA, USA and National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Panos Roussos
Alisa Timashpolsky
Mihaela Barbu
Sergei Rudchenko
Marina Bibikova
Brandy Klotzle
William Byne
Rebecca Lyddon
Antonio Fabio Di Narzo
Yasmin L Hurd
Eugene V Koonin
Stella Dracheva

Funding

Comparative Analysis Of Completely Sequenced GenomesZIALM000073 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$43.1M
The Opioid mesolimbic system in heroin abuseR01DA015446 · NIDA · KAROLINSKA INSTITUTE · PI HURD, YASMIN L. · 2002 to 2018
$7.1M
RNA editing in suicide, major depression and animal model of depressionR21MH090352 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DRACHEVA, STELLA · 2010 to 2011
$379k
Probing the Link between RNA Editing and Drug AddictionR21DA031557 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI DRACHEVA, STELLA · 2011 to 2012
$352k
Genetic and Molecular Determinants of SuicideI01BX001829 · VA · JAMES J PETERS VA MEDICAL CENTER · PI DRACHEVA, STELLA · 2014 to 2016
–
Dissecting Cis Regulation of Gene Expression in SchizophreniaI01BX002395 · VA · JAMES J PETERS VA MEDICAL CENTER · PI ROUSSOS, PANAGIOTIS · 2014 to 2022
–
BLRD VA I01 BX001829BLRD VA I01 BX002395NIDA NIH HHS R01 DA015446NIDA NIH HHS R21DA031557NIMH NIH HHS R21MH090352
6 · The paper itself

Abstract

We applied Illumina Human Methylation450K array to perform a genomic-scale single-site resolution DNA methylation analysis in neuronal and nonneuronal (primarily glial) nuclei separated from the orbitofrontal cortex of postmortem human brain. The findings were validated using enhanced reduced representation bisulfite sequencing. We identified thousands of sites differentially methylated (DM) between neuronal and nonneuronal cells. The DM sites were depleted within CpG-island-containing promoters but enriched in predicted enhancers. Classification of the DM sites into those undermethylated in neurons (neuronal type) and those undermethylated in nonneuronal cells (glial type), combined with findings of others that methylation within control elements typically negatively correlates with gene expression, yielded large sets of predicted neuron-specific and non-neuron-specific genes. These sets of predicted genes were in excellent agreement with the available direct measurements of gene expression in human and mouse. We also found a distinct set of DNA methylation patterns that were unique for neuronal cells. In particular, neuronal-type differential methylation was overrepresented in CpG island shores, enriched within gene bodies but not in intergenic regions, and preferentially harbored binding motifs for a distinct set of transcription factors, including neuron-specific activity-dependent factors. Finally, non-CpG methylation was substantially more prevalent in neurons than in nonneuronal cells.

Indexed as

DNA MethylationEnhancer Elements, GeneticAdultAnimalsBinding SitesBrainCell NucleusCpG IslandsEvolution, MolecularGene ExpressionGenome, HumanHumansMaleMiceNeurogliaNeuronsTranscription Factors

Identifiers

PMID24057217
PMCPMC3874157

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.