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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, 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]
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“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]
In the citing paper
“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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Kumar, D. B. U., Aggarwal, M., Kaas, G. A., Lewis, J., Wang, J., Ross, D. L., Zhong, C., Kennedy, A. J., Song, H., & Sweatt, J. D. (2015) · Neuroepigenetics · doi:10.1016/j.nepig.2015.10.002 · Cited by 49
A Comprehensive Analysis of Cell Type–Specific Nuclear RNA From Neurons and Glia of the Brain
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Dynamic DNA methylation controls glutamate receptor trafficking and synaptic scaling
Sweatt, J. D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13564 · Cited by 52
Sølvsten, C. A. E., de Paoli, F. V., Christensen, J., & Nielsen, A. L. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-0344-y · Cited by 55
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Physical Exercise and Epigenetic Modulation: Elucidating Intricate Mechanisms
Sanchis-Gomar, H. P.-G., & a-Gimenez, J. G. ́. (2014) · Cited by 51
Sperm Functional Genome Associated With Bull Fertility
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Klein, H.-U., Bennett, D. A., & De Jager, P. L. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1612-7 · Cited by 49
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TET enzymatic oxidation of 5-methylcytosine, 5-hydroxymethylcytosine and 5-formylcytosine
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Simultaneous single-cell analysis of 5mC and 5hmC with SIMPLE-seq
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“Considering that the average abundance of 5hmC is approximately 10% or less of 5mC 56 and the specificity of the two labeling approaches, it is optimal to perform 5hmC labeling before the 5mC reaction for high specificity.”
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Metadata
- 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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