Kriaucionis Skirmantas, Heintz Nathaniel
Laboratory of Molecular Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10065, USA.
Science. 2009 May 15;324(5929):929-30. doi: 10.1126/science.1169786. Epub 2009 Apr 16.
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.
尽管表观遗传调控在神经系统疾病中具有重要作用,但人们对神经元染色质却知之甚少。小脑浦肯野神经元具有大而呈常染色质的细胞核,而颗粒细胞核则小且具有更典型的异染色质分布。在比较浦肯野细胞核和颗粒细胞核中5-甲基胞嘧啶的丰度时,我们检测到一种不寻常的DNA核苷酸的存在。通过薄层色谱、高压液相色谱和质谱分析,我们将该核苷酸鉴定为5-羟甲基-2'-脱氧胞苷(hmdC)。hmdC在浦肯野细胞中占总核苷酸的0.6%,在颗粒细胞中占0.2%,而在癌细胞系中不存在。hmdC是核DNA的一个组成部分,在大脑中含量很高,这表明它在神经元功能的表观遗传控制中发挥作用。