CGIs are characterised by elevated CpG density and GC content [10,11,14,74], transcription factor binding sites (TFBS) [42–46], and G quadruplex (G4) DNA sequences [47–49,52,53]. CGIs overlap key gene regulatory elements, such as promoters [2,4,5,27,113,114] and enhancers [6,7,9] and can thus switch between active/poised and repressive chromatin states, depending on the activity of the gene which they are regulating. These states are influenced by the complement of so called ‘reader' proteins targeted to CGIs, which include transcriptional activators (CBP/P300, SETD1, CFP1, TET1, KDM2A, RNAP2) and repressors (PRC1, PRC2, KDM2B) [6,9,23,28,30,38,39,81–84,110–112]. In exceptional cases, such as in imprinted control regions (ICRs), or cancer testis antigen gene (CTA) promoters, CGIs can be stably silenced through DNA methylation (5mC) and methyl-CpG binding proteins (MBDs), a state which is reinforced by constant targeting of DNA methyltrasferases (DNMTs) [3,24,25,56,61,62]. It is not yet clear how continuous presence of 5mC within CGIs influences G4 sequences [52].