Introduction--Epiphanies in epigenetics.

The combinatorial pattern of DNA and histone modifications and their associated histone variants constitute an epigenetic code that shapes gene expression patterns by increasing or decreasing the transcriptional potential of genomic domains. The epigenetic coding status, at any given chromosomal location, is subject to modulation by noncoding RNAs and remodeling complexes. DNA methylation is associated with histone modifications, particularly the absence of histone H3 lysine 4 methylation (H3K4me0) and the presence of histone H3 lysine 9 methylation (H3K9m). We briefly discuss four protein domains (ADD, CXXC, MBD, and SRA), and the functional implications of their architecture in linking histone methylation to that of DNA in mammalian cells. We also consider the domain structure of the DNA methyltransferase DNMT1, its accessory protein UHRF1, and their associated proteins. Finally, we discuss a mechanism by which methylation of DNA and of histones may be coordinately maintained during mitotic cell division, allowing for the transmission of parental methylation patterns to newly replicated chromatin.