Figure 3: Transcriptionally-relevant changes to DNA that do not affect DNA sequence. (A) Cytosine methylation. CpG doublets are presented as square boxes (open is unmethylated; filled red is methylated cytosine). CpG islands, which are located proximal to ∼60% of mammalian promoters, are typically unmethylated. In the cartoon, a DNA methyltransferase (DNMT) catalyzes de novo methylation at the CpG island, recruiting a CpG “methyl-binding domain” (MBD) which in turn recruits other factors to repress transcription. CpG methylation can also directly prevent recognition by DNA-binding proteins (not shown). (B) Alternative DNA configurations that can form at select repeating sequences, in this case mirror-symmetric homopurine-homopyrimidine stretches. Such elements can form triplex H-DNA via interactions with each repeat, or G-quartets (G4-DNA) via interactions with G residues in each repeat-half. Both structures result in the formation of stretches of single-stranded DNA that confer enhanced sensitivity to S1 nuclease, a common probe for their formation in vivo. Modified from [182].