A recurrent theme in eukaryotic genome regulation stipulates that the properties of DNA are strongly influenced by the nucleoprotein complex into which it is assembled. Methylation of cytosine residues in vertebrate genomes has been implicated in influencing the assembly of locally repressive chromatin architecture. Current models suggest that covalent modification of DNA results in heritable, long‐term transcriptional silencing. In October of 2003, two manuscripts1,2 were published that challenge important aspects of this model, suggesting that modulation of both DNA methylation itself, (...) as well as the machinery implicated in its interpretation, are involved in acute gene regulation. BioEssays 26:217–220, 2004. © 2004 Wiley Periodicals, Inc. (shrink)