The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
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]
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“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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The importance of epigenetics in diagnostics and treatment of major depressive disorder
Czarny, P., Białek, K., Ziółkowska, S., Strycharz, J., Barszczewska, G., & Sliwinski, T. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11030167 · Cited by 37
Measurement of oxidatively generated base damage to nucleic acids in cells: facts and artifacts
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BackgroundDNA Epigenetics in Addiction Susceptibility
Kaplan, G., Xu, H., Abreu, K., & Feng, J. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.806685 · Cited by 34
“Regional and agedependent changes in hmC were observed when assessing hmC dynamics in mouse hippocampal and cerebellar neurons during early-life, adolescence/early adulthood, and middle-age (Kriaucionis and Heintz, 2009; Szulwach et al., 2011).”
BackgroundLaan, L., Klar, J., Sobol, M., Hoeber, J., Shahsavani, M., Kele, M., Fatima, A., Zakaria, M., Annerén, G., Falk, A., et al. (2020) · Clinical Epigenetics · doi:10.1186/s13148-019-0803-1 · Cited by 33
TET-TDG active DNA demethylation at CpG and non-CpG sites
DeNizio, J. E., Dow, B. J., Serrano, J. C., Ghanty, U., Drohat, A. C., & Kohli, R. M. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.166877 · Cited by 32
Perinatal stress and epigenetics.
(2021) · Handbook of Clinical Neurology · doi:10.1016/b978-0-12-820107-7.00008-2 · Cited by 28
Hamilton, P. J., Lim, C. J., Nestler, E. J., & Heller, E. A. (2018) · Methods in Molecular Biology · doi:10.1007/978-1-4939-7774-1_5 · Cited by 28
A nervous predisposition to unrepaired DNA double strand breaks
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The molecular basis of depression: implications of sex-related differences in epigenetic regulation
Kawatake-Kuno, A., Murai, T., & Uchida, S. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.708004 · Cited by 23
“The brain shows a 10-fold enrichment of 5hmC compared to peripheral tissues, and it is associated with neuronal plasticity (Kriaucionis and Heintz, 2009; Szulwach et al., 2011).”
BackgroundHack, L. M., Dick, A. L. W., & Provençal, N. (2016) · Environmental Epigenetics · doi:10.1093/eep/dvw016 · Cited by 18
Vaher, K., Anier, K., Jürgenson, M., Harro, J., & Kalda, A. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120916137 · Cited by 12
“In addition, it has been demonstrated that ten-eleven translocation enzymes (Tet1–3) are able to catalyse the addition of the hydroxyl group onto the methyl group of 5-mC to form 5-hydroxymethylcytosine (5-hmC), therefore participating in active DNA demethylation (Ito et al., 2011; Kriaucionis and Heitz, 2009).”
Background
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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