Evidence map›Paper›PMID 22961382›Full record

ArticleNature structural & molecular biology2012

5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary.

Tarang Khare, Shraddha Pai, Karolis Koncevicius, Mrinal Pal, Edita Kriukiene, Zita Liutkeviciute, Manuel Irimia, Peixin Jia, Carolyn Ptak, Menghang Xia and 13 more

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.

0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed
11.4field-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

157 citing papers in PubMed, 246 citations in OpenAlex.

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  13. DNA Methylation in Long-Term Memory.Physiology (Bethesda, Md.) · 2025
    Review
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  16. Article
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  19. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  20. Article

97 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

23 authors at 10 institutions in 6 countries.

Tarang KhareThe Krembil Family Epigenetics Laboratory, The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Shraddha Pai
Karolis Koncevicius
Mrinal Pal
Edita Kriukiene
Zita Liutkeviciute
Manuel Irimia
Peixin Jia
Carolyn Ptak
Menghang Xia
Raymond Tice
Mamoru Tochigi
Solange Moréra
Anaies Nazarians
Denise Belsham
Albert H C Wong
Benjamin J Blencowe
Sun Chong Wang
Philipp Kapranov
Rafal Kustra
Viviane Labrie
Saulius Klimasauskas
Arturas Petronis
Centre for Addiction and Mental Health · CAUniversity of Toronto · CAVilnius University · LTLaboratoire d'Enzymologie et Biochimie Structurales · FRNational Center for Advancing Translational Sciences · USNational Central University · TWNational Institute of Environmental Health Sciences · USPublic Health Ontario · CASt. Laurent Institute · USThe University of Tokyo · JP

Funding

DNA METHYLOME ANALYSIS IN BIPOLAR DISORDERR01MH088413 · NIMH · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI PETRONIS, ART · 2009 to 2013
$4.1M
DNA METHYLOME STUDY IN TYPE 1 DIABETESDP3DK085698 · NIDDK · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI PETRONIS, ART · 2009 to 2009
$3.1M
Molecular Epigenetic Studies of Major DepressionR01MH074127 · NIMH · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI PETRONIS, ART · 2005 to 2009
$1.3M
Approaches for genomic mapping of 5-hydroxymethylcytosine a novel epigenetic marR21HG005758 · NHGRI · INSTITUTE OF BIOTECHNOLOGY · PI KLIMASAUSKAS, SAULIUS · 2010 to 2011
$299k
Methylome Profiling via DNA Methyltransferase-directed LabelingR21HG004535 · NHGRI · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI PETRONIS, ART · 2008 to 2009
$297k
CIHR 186007CIHR 199170NHGRI NIH HHS HG004535NHGRI NIH HHS HG005758NHGRI NIH HHS R21 HG004535NHGRI NIH HHS R21 HG005758NIDDK NIH HHS DP3 DK085698NIDDK NIH HHS DP3DK085698NIMH NIH HHS MH074127NIMH NIH HHS MH088413NIMH NIH HHS R01 MH074127NIMH NIH HHS R01 MH088413
6 · The paper itself

Abstract

The 5-methylcytosine (5-mC) derivative 5-hydroxymethylcytosine (5-hmC) is abundant in the brain for unknown reasons. Here we characterize the genomic distribution of 5-hmC and 5-mC in human and mouse tissues. We assayed 5-hmC by using glucosylation coupled with restriction-enzyme digestion and microarray analysis. We detected 5-hmC enrichment in genes with synapse-related functions in both human and mouse brain. We also identified substantial tissue-specific differential distributions of these DNA modifications at the exon-intron boundary in human and mouse. This boundary change was mainly due to 5-hmC in the brain but due to 5-mC in non-neural contexts. This pattern was replicated in multiple independent data sets and with single-molecule sequencing. Moreover, in human frontal cortex, constitutive exons contained higher levels of 5-hmC relative to alternatively spliced exons. Our study suggests a new role for 5-hmC in RNA splicing and synaptic function in the brain.

Indexed as

5-MethylcytosineAlternative SplicingAnimalsBrainCell LineCytosineGlucosyltransferasesHumansIntronsMaleMiceMice, Inbred C57BLMicroarray AnalysisOrgan SpecificityReproducibility of ResultsRNA Splicing5-hydroxymethylcytosine5-MethylcytosineCytosineGlucosyltransferases

Identifiers

PMID22961382
PMCPMC3465469
OpenAlexW2047246007

What OpenQuestion holds

Textmetadata
LicenceTDM
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.