The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Open accessAbstract
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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5-hydroxymethylcytosine is produced by the addition of hydroxyl groups to 5-methylcytosine under the action of the ten-eleven translocation (TET) enzymes.
“5-hydroxymethylcytosine, which is produced by the addition of hydroxyl groups to 5-methylcytosine under the action of the ten-eleven translocation (TET) enzymes (Fig. 2).59,60”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [60]
The passage labeled Abstract (page not supplied) identifies 5-hydroxymethylcytosine and describes its hydroxylated methyl group, but treats its role in oxidative demethylation as a possibility. It does not identify TET enzymes or establish that they produce 5-hydroxymethylcytosine from 5-methylcytosine. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThis nucleolar signal enables FANS purification of target nuclei for assessment of DNA, nascent RNA transcription, and proteomic analysis of histone modifications or transcription factor binding.
“This enables FANS purification of target nuclei for assessment of DNA, nascent RNA transcription in the specific cell-type of interest, as well as proteomic analysis of histone modifications or transcription factor binding120,121.”
From Decoding neuroproteomics: integrating the genome, translatome and functional anatomy (2014) · cites this paper as [121]
Neurons have high levels of hydroxymethylcytosine (hmC), a derivative of mC that may have distinct functional roles.
“First, neurons have high levels of hydroxymethylcytosine (hmC), a derivative of mC that may have distinct functional roles (Kriaucionis and Heintz, 2009; Mellén et al., 2017).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Kriaucionis and Heintz, 2009
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- 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
- Published
- 2009-05-15
- Volume
- 324
- Issue
- 5929
- Pages
- 929-930
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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