Cited by 2,700Epigenetics and DNA MethylationRNA modifications and cancerDNA and Nucleic Acid Chemistry

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The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain

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Kriaucionis, Skirmantas, Heintz, Nathaniel·2009·Science

DOI 10.1126/science.1169786PMC PMC3263819

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Abstract

Despite the importance of epigenetic regulation in neurological disorders, little is known about neuronal chromatin. Cerebellar Purkinje neurons have large and euchromatic nuclei, whereas granule cell nuclei are small and have a more typical heterochromatin distribution. While comparing the abundance of 5-methylcytosine in Purkinje and granule cell nuclei, we detected the presence of an unusual DNA nucleotide. Using thin-layer chromatography, high-pressure liquid chromatography, and mass spectrometry, we identified the nucleotide as 5-hydroxymethyl-2'-deoxycytidine (hmdC). hmdC constitutes 0.6% of total nucleotides in Purkinje cells, 0.2% in granule cells, and is not present in cancer cell lines. hmdC is a constituent of nuclear DNA that is highly abundant in the brain, suggesting a role in epigenetic control of neuronal function.

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“This issue is especially relevant for the hippocampal DMRs, as hmC modifications are highly abundant in the brain.(86) Additional chemical modifications using potassium perruthenate (KRuO4, oxBS-Seq) or enzymatic modifications of DNA using b-glucosyltransferases and TET (TAB-Seq) are needed to resolve mC from hmC.”
Background
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“The transient nature of 5hmC is still debated based on evidence that only 1% of all cytosines in the mammalian brain are hydroxymethylated [98], but there is nevertheless evidence for unique regulatory effects of 5hmC compared to 5mC.”
Background

Authors: Kriaucionis, S., & Heintz, N.
Affiliations: Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Howard Hughes Medical Institute (US)
Corresponding author: Heintz, Nathaniel
ORCID: Heintz, Nathaniel
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2009-05-15
Volume: 324
Issue: 5929
Pages: 929-930
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1169786
PMC: PMC3263819
OpenAlex: W2152451432
Cited by: 2,700
References: 14
Citations by year: 2026: 53 · 2025: 69 · 2024: 84 · 2023: 93 · 2022: 112 · 2021: 137 · 2020: 107 · 2019: 150 · 2018: 190 · 2017: 218 · 2016: 236 · 2015: 220 · 2014: 259 · 2013: 252 · 2012: 202
FWCI: 69.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords: 5-hydroxymethylcytosine, Purkinje cells, cerebellar granule cells, DNA methylation, epigenetic regulation, brain DNA, nucleotide composition
MeSH terms: Animals, Brain Chemistry, Cell Line, Cerebellum, Chromatography, High Pressure Liquid, Chromatography, Thin Layer, Cytosine, Deoxycytidine, DNA, DNA Damage, Humans, Purkinje Cells, Mass Spectrometry, 5-Methylcytosine, Mice

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The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain

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