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

• Published in: Science (American Association for the Advancement of Science) Vol. 324; no. 5929; pp. 929 - 930
• Main Authors: Kriaucionis, Skirmantas, Heintz, Nathaniel
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15-05-2009; The American Association for the Advancement of Science
• Subjects: 5-Methylcytosine - analogs & derivatives; Animals; Biological and medical sciences; Brain; Brain Chemistry; Cell Line; Cell lines; Cell nucleus; Cellular biology; Cerebellum - chemistry; Cerebellum - cytology; Chromatin; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Cytosine - analogs & derivatives; Cytosine - analysis; Deoxycytidine - analogs & derivatives; Deoxycytidine - analysis; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA Damage; Epigenetics; Fundamental and applied biological sciences. Psychology; Humans; Mass Spectrometry; Mice; Neurons; Nucleic acids; Nucleosides; Nucleotides; Purkinje cells; Purkinje Cells - chemistry; Vertebrates: nervous system and sense organs; Cerebellum; Chromatin; Cell line; Granule neuron; DNA; Central nervous system; Distribution; Purkinje neuron; Neurological disorder; Mass spectrometry; Encephalon
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1169786

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.