Direct single nucleotide mapping of genomic CpG marks

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DESCRIPTION (provided by applicant): Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is DNA methylation. In the mammalian genome, cytosines (C) were long known to exist in two functional states: unmethylated or methylated at the 5-position of the pyrimidine ring (5mC). Recent studies of genomic DNA from the human and mouse brain, neurons and from mouse embryonic stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethylcytosine (hmC) by the action of oxygenases. These findings provided important clues in a long elusive mechanism of active DNA demethylation and bolstered a fresh wave of studies in the area of epigenetic regulation in mammals. However, such studies are hindered by the shortcomings of available experimental techniques for genome-wide epigenome analysis. This project is dedicated to developing a break-through technique for genome-wide analysis of the modification status of CpG dinucleotides that combines single-base resolution with targeted and economic sequencing of the genome.