Abstract

DNA methylation acts as an epigenetic modification in vertebrate DNA. Recently it has become clear that the DNA and histone lysine methylation systems are highly interrelated and rely mechanistically on each other for normal chromatin function in vivo. Here we examine some of the functional links between these systems, with a particular focus on several recent discoveries suggesting how lysine methylation may help to target DNA methylation during development, and vice versa. In addition, the emerging role of non-methylated DNA found in CpG islands in defining histone lysine methylation profiles at gene regulatory elements will be discussed in the context of gene regulation. This article is part of a Special Issue entitled: Methylation: A Multifaceted Modification — looking at transcription and beyond.Graphical abstractHighlights•There is an emerging realisation that DNA and histone lysine methylation in mammals are highly interrelated.•Targeting of DNA methylation is mechanistically linked to H3K9 methylation.•Uhrf1 acts as a link between H3K9 methylation and maintenance methylation during DNA replication.•Targeting of Dnmt3a/b is influenced by H3K4 and H3K36 methylation.•Non-methylated DNA at CpG islands influences histone methylation through ZF-CxxC proteins.