DNA methylation: a historical perspective

In 1925, 5-methylcytosine was first reported in bacteria. However, its biological importance was not intuitive for several decades. After this initial lag, the ubiquitous presence of this methylated base emerged across all domains of life and revealed a range of essential biological functions. Today, we are armed with the knowledge of the key factors that establish, maintain, and remove DNA methylation and have access to a staggering and rapidly growing number of base-resolution methylation maps. Despite this, several fundamental details about the precise role and interpretation of DNA methylation patterns remain under investigation. Here, we review the field of DNA methylation from its beginning to present day, with an emphasis on findings in mammalian systems, and point the reader to select experiments that form the foundation of this field.