CpG island chromatin: a platform for gene regulation

Abstract

The majority of mammalian gene promoters are encompassed within regions of the genome called CpG islands that have an elevated level of non-methylated CpG dinucleotides. Despite over 20 years of study, the precise mechanisms by which CpG islands contribute to regulatory element function remain poorly understood. Recently it has been demonstrated that specific histone modifying enzymes are recruited directly to CpG islands through recognition of non-methylated CpG dinucleotide sequence. These enzymes then impose unique chromatin architecture on CpG islands that distinguish them from the surrounding genome. In the context of this work we discuss how CpG island elements may contribute to the function of gene regulatory elements through the utilization of chromatin and epigenetic processes.

Figure 1

The various chromatin states of CpG islands. CpG islands have the capacity to adopt multiple chromatin states each with varying propensities for gene activation or repression (see main text for a description of these). Central to the capability of CpG islands to adopt and transition between these states is the default permissive state (A), partly imposed by the ZF-CxxC proteins KDM2A and CFP1. Nucleosomes within CpG islands are depicted in green and nucleosomes outside of CpG islands are grey. Straight arrows represent pathways of transition between individual CpG island states. Circular arrow represents a cell cycle involving initiation of DNA replication from CpG island ORIs.