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Cited by 375Epigenetics and DNA MethylationGenomics and Chromatin DynamicsRNA modifications and cancer

Genomic mapping of 5-hydroxymethylcytosine in the human brain

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Jin, Seung-Gi, Wu, Xiwei, Li, Arthur X., Pfeifer, Gerd P.·2011·Nucleic Acids Research
DOI 10.1093/nar/gkr120PMC PMC3130285
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Abstract

Methylation at the 5-position of cytosine is a well-studied epigenetic pathway. In addition to 5-methylcytosine (5mC), substantial amounts of 5-hydroxymethylcytosine (5hmC) also referred to as the sixth DNA base have been detected in certain tissues, most notably the brain. However, the genomic distribution of this cytosine modification is unknown. Here, we have used an immunoprecipitation technique (5hmC-IP) to examine the occurrence of 5hmC in DNA from human brain frontal lobe tissue. The distribution of 5hmC was compared to that of 5mC. We show that 5hmC is more selectively targeted to genes than is 5mC. 5hmC is particularly enriched at promoters and in intragenic regions (gene bodies) but is largely absent from non-gene regions. 5hmC peaks at transcription start sites did not correlate with gene expression levels for promoters with intermediate or high CpG content. However, the presence of 5hmC in gene bodies was more positively correlated with gene expression levels than was the presence of 5mC. Promoters of testis-specific genes showed strong 5mC peaks in brain DNA but were almost completely devoid of 5hmC. Our data provide an overview of the genomic distribution of 5hmC in human brain and will set the stage for further functional characterization of this novel DNA modification.

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Authors
Jin, S.-G., Wu, X., Li, A. X., & Pfeifer, G. P.
Affiliations
City Of Hope National Medical Center (US)
Corresponding author
Pfeifer, Gerd P.
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2011-03-04
Volume
39
Issue
12
Pages
5015-5024
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkr120
PMC
PMC3130285
OpenAlex
W2146301715
Cited by
375
References
3
Citations by year
2026: 6 · 2025: 14 · 2024: 14 · 2023: 15 · 2022: 8 · 2021: 13 · 2020: 15 · 2019: 17 · 2018: 24 · 2017: 31 · 2016: 30 · 2015: 26 · 2014: 45 · 2013: 53 · 2012: 44
FWCI
21.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (AG036041, R01AG036041)
  • National Cancer Institute (CA 084469, R01CA084469)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
5-hydroxymethylcytosine, DNA methylation, 5-methylcytosine, genomic distribution, human brain, frontal lobe, promoter enrichment, gene expression, CpG content, testis-specific genes, DNA modification
MeSH terms
Animals, Brain Chemistry, Cytosine, DNA, Humans, Promoter Regions, Genetic, Gene Expression, Genomics, 5-Methylcytosine, Mice

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