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Reports
Submitted on December 15, 2008 The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
1 Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA. * To whom correspondence should be addressed.
In spite of the importance of epigenetic regulation in neurological disorders, little is known about neuronal chromatin. Cerebellar Purkinje neurons have large and euchromatic nuclei, whilst granule cell nuclei are small and have a more typical heterochromatin distribution. While comparing the abundance of 5-methylcytosine (mC) in Purkinje and granule cell nuclei, we detected the presence of an unusual DNA nucleotide. Using thin layer chromatography (TLC), high pressure liquid chromatography (HPLC), and mass spectrometry (MS), we have identified the nucleotide as 5-hydroxymethyl-2-deoxycytidine (hmdC). hmdC comprises 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 enriched in the brain, suggesting a role in epigenetic control of neuronal function.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)