Evidence map›Paper›PMID 26046694›Full record

ArticleEpigenetics2015

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood.

Arko Sen, Pablo Cingolani, Marie-Claude Senut, Susan Land, Adriana Mercado-Garcia, Martha M Tellez-Rojo, Andrea A Baccarelli, Robert O Wright, Douglas M Ruden

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
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  14. Article
  15. Sex-Specific Alterations in Cardiac DNA Methylation in Adult Mice by Perinatal Lead Exposure.International journal of environmental research and public health · 2021
    Article
  16. Review
  17. Article
  18. Review
  19. Neonatal Lead (Pb) Exposure and DNA Methylation Profiles in Dried Bloodspots.International journal of environmental research and public health · 2020
    Article
  20. Epigenetic Basis of Lead-Induced Neurological Disorders.International journal of environmental research and public health · 2020
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 5 countries.

Arko Sena Institute of Environmental Health Sciences; Wayne State University ; Detroit , MI , USA.
Pablo Cingolani
Marie-Claude Senut
Susan Land
Adriana Mercado-Garcia
Martha M Tellez-Rojo
Andrea A Baccarelli
Robert O Wright
Douglas M Ruden
Wayne State University · USNational Institute of Public Health · SICentre For Human Genetics · INIcahn School of Medicine at Mount Sinai · USMassachusetts Department of Public Health · US

Funding

Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI SUSAN A KORRICK · 1985 to 2026
$44.6M
The Mount Sinai Transdisciplinary Center on Early Environmental ExposuresP30ES023515 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Maria Jose Rosa · 2014 to 2026
$21.3M
Stress, Lead, Iron Deficiency and NeurodevelopmentR01ES013744 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Robert O Wright · 2007 to 2026
$13.4M
Pilot Project ProgramP30ES020957 · NIEHS · WAYNE STATE UNIVERSITY · PI PARKER, GRAHAM C · 2014 to 2021
$10.1M
QTL AND MICROARRAY MAPPING LEAD SENSITIVITY GENESR01ES012933 · NIEHS · WAYNE STATE UNIVERSITY · PI RUDEN, DOUGLAS M · 2004 to 2015
$3.4M
BPA, Phthalates & Stress: Mechanisms and Interactions for Childhood ObesityR01ES021357 · NIEHS · HARVARD SCHOOL OF PUBLIC HEALTH · PI BACCARELLI, ANDREA, WRIGHT, ROBERT O · 2012 to 2016
$3.3M
Environment, Fetal Tissue DNA Methylation & BirthweightR01ES020268 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BACCARELLI, ANDREA, WRIGHT, ROBERT O · 2011 to 2013
$2.5M
NIEHS NIH HHS P30ES020957NIEHS NIH HHS P30ES023515NIEHS NIH HHS R01ES012933NIEHS NIH HHS R01ES013744NIEHS NIH HHS R01ES020268NIEHS NIH HHS R01ES021357NIEHS NIH HHS R21ES021893
6 · The paper itself

Abstract

Prenatal exposure to neurotoxicants such as lead (Pb) may cause stable changes in the DNA methylation (5mC) profile of the fetal genome. However, few studies have examined its effect on the DNA de-methylation pathway, specifically the dynamic changes of the 5-hydroxymethylcytosine (5hmC) profile. Therefore, in this study, we investigate the relationship between Pb exposure and 5mC and 5hmC modifications during early development. To study the changes in the 5hmC profile, we use a novel modification of the Infinium™ HumanMethylation450 assay (Illumina, Inc.), which we named HMeDIP-450K assay, in an in vitro human embryonic stem cell model of Pb exposure. We model Pb exposure-associated 5hmC changes as clusters of correlated, adjacent CpG sites, which are co-responding to Pb. We further extend our study to look at Pb-dependent changes in high density 5hmC regions in umbilical cord blood DNA from 48 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. For our study, we randomly selected umbilical cord blood from 24 male and 24 female children from the 1st and 4th quartiles of Pb levels. Our data show that Pb-associated changes in the 5hmC and 5mC profiles can be divided into sex-dependent and sex-independent categories. Interestingly, differential 5mC sites are better markers of Pb-associated sex-dependent changes compared to differential 5hmC sites. In this study we identified several 5hmC and 5mC genomic loci, which we believe might have some potential as early biomarkers of prenatal Pb exposure.

Indexed as

5-MethylcytosineCell LineCpG IslandsCytosineDNA MethylationEnvironmental ExposureFetal BloodHuman Embryonic Stem CellsHumansLeadMexicoSequence Analysis, DNASex FactorsUmbilical Cord5-hydroxymethylcytosine5-MethylcytosineCytosineLead5-hydroxymethylcytosine5-methylcytosineAclustA-clustering approach for grouping HM450K CpG sites into clusters based on correlationsclustersCpG island, CpG islands are usually in the promoter and 5' untranslated regions of genesCpG islandsCpG, sites, CG dinucleotide methylation site in the genome corresponding with probes on HM450KDhMRs, Differentially Hydroxymethylated regions (clusters) identified by GEEDMRs, Differentially methylated regions (clusters) identified by GEEELEMENT, Early Life Exposure in Mexico to Environmental ToxicantsGEE, Generalized Estimating Equations, used to measure the estimated change in DNA methylation in co-regulated regions of the genomeHM450KHM450K, Infinium Human Methylation 450K BeadChip array from IlluminaHMeDIP-450KHMeDIP-450K, Infinium Human Methylation 450K BeadChip array from Illumina coupled with immunoprecipitation with 5hmC antibodieshMRs, Hydroxymethylated regions (clusters) identified by A-clusteringleadLINE-1, Long Interspersed Element 1, a common retrotransposon in humansMRs, Methylation regions (clusters) identified by A-clusteringumbilical cord blood

Identifiers

PMID26046694
PMCPMC4623482
OpenAlexW1883623951

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.