DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

DNA methylation is a major epigenetic process that regulates chromatin structure which causes transcriptional activation or repression of genes in a context-dependent manner. In general, DNA methylation takes place when methyl groups are added to the appropriate bases on the genome by the action of writer molecules known as DNA methyltransferases. How these methylation marks are read and interpreted into different functionalities represents one of the main mechanisms through which the genes are switched ON or OFF and typically involves different types of reader proteins that can recognize and bind to the methylated regions. A tightly balanced regulation exists between the writers and readers in order to mediate normal cellular functions. However, alterations in normal methylation pattern is a typical hallmark of cancer which alters the way methylation marks are written, read and interpreted in different disease states. This unique characteristic of DNA methylation readers has identified them as attractive therapeutic targets. In this review, we describe the current state of knowledge on the different classes of DNA methylation readers identified thus far along with their normal biological functions, describe how they are dysregulated in cancer, and discuss the various anti-cancer therapies that are currently being developed and evaluated for targeting these proteins.