Genome-wide DNA methylation in human heart failure

Abstract

Rapidly advancing high-throughput sequencing technology is now bringing attention to many basic biological aspects of the human genome. DNA methylation refers to the epigenetic modification of cytosine nucleotides by a methyl group that occurs throughout the genome. Owing to its significant influence on protein–DNA interactions and subsequent gene-expression control, some scientists call methylated-cytosines ‘the 5th nucleotide’. We recently reported the first evidence of differential DNA methylation in human heart failure. Altered DNA methylation and a change in the expression of proximal genes have also been demonstrated in atherosclerotic plaques. For other diseases such as psychosis and cancer, the role of DNA methylation on disease pathogenesis and progression has already been shown and forms the target for new drug therapy. Understanding this aspect of disease biology may therefore contribute to the heart failure drug discovery pipeline. In this article, we summarize the basic biology of DNA methylation and discuss its implications in complex diseases such as heart failure.