Classically, the function of DNA methylation at 5-methyl-cytosine (5mC) has been associated with regulatory regions located mainly at gene promoters with high density of CpG sites, termed CpG islands. These well characterized regions have been shown to control gene expression. However, 5mC is also found within gene bodies. While the function of gene body methylation has not be clearly defined, it is associated with regulation of co-transcriptional processes.  Therefore, changes in 5mC distribution in gene bodies can deregulate co-transcriptional process, impacting the malignant cell phenotype.

By leveraging simultaneous capture of genotypes and transcriptional profiles directly from human samples, we aim to define the consequences of disruption of DNA methylation, to identify its functional consequences driving clonal expansions in the blood and reshaping the cell differentiation landscape.