Fig. 2.

Methylation of the DNA. Cytosines located proximal to guanines are the target of methylation by the DNA methyl transferase (DNMT) enzymes. Two classes of DNMT’s, DNMT1 and DNMT3, mediate maintenance versus de novo methylation. Increased methylation of cytosines can alter gene transcription directly by sterically hindering the access of transcription factors, or indirectly by recruiting methyl-binding domain (MBD) proteins, the most famous of which is MeCP2. Some MBDs, such as Kaiso, are also capable of binding to unmethylated DNA and recruiting DNMT activity. The relationship between cytosine methylation and gene expression is not as straightforward as that for changes to the histones.