Abstract
the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression. Conclusions: i) We for the first time demonstrate that genomic DNA from adult human liver contains a significant amount of 5hmC (0,10 – 0,63% from total cytosine); ii) 5hmC in hepatocytes is enriched in actively transcribed genes, as well as in enhancers. Thus, 5hmC might be an important determinant for the interindividual differences in drug metabolism and toxicity; iii) The usage of traditional bisulfite sequencing in epigenetic studies on human liver should be avoided, since it strongly underestimates the actual variability of DNA methylation; iv) Tet1-assisted bisulfite sequencing (TAB-Seq) was combined with Agilent Methyl-SEQ platform for targeted NGS. The resultant TAB-Methyl-SEQ method allows to analyze the absolute 5mC and 5hmC values at multiple CpG sites in ADME genes of interest. Abundance and distribution of hydroxymethylcytosine (5hmC) in human liver Maxim Ivanov1, Mart Kals4, Marina Kacevska1, Isabel Barragan1, Kie Kasuga2, Anders Rane3, Andres Metspalu4,5,6, Lili Milani4,6, Magnus Ingelman-Sundberg1
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