The correlation between DNA methylation and chromatin structure, as it relates to transcriptional activity, is demonstrated by the observation that there are several proteins, that bind to methylated CpGs but not to unmethylated CpGs, whose functions are integrated into transcriptional regulation. There are currently 15 genes in the human genome that encode proteins that bind to methyl-CpG in DNA. These 15 proteins are divided into 3 subfamilies identified by structural similarities. These sub-families are the methyl binding domain (MBD) proteins, the methyl-CpG-binding zinc finger proteins (also called the Kaiso family), and the SRA domain ( S ET and R ING finger domain A ssociated) containing proteins. The SET domain is so-called because it was first identified in three Drosophila proteins called S uppressor of variegation variant 3-9 [Su(var)3-9], E nhancer of zeste, and T rithorax. The RING domain is a zinc-finger-like domain which gets its name from the term R eally I nteresting N ew G ene.
Many positively controlled promoters, such as the lac promoter, are not fully functional in the presence of RNAp alone and require activation by CAP. CAP is encoded by a separate Regulatory gene, and is present in constitutive levels. CAP is active only in the presence of cAMP. The binding of cAMP to CAP causes a conformational change in the protein allowing it to bind to the promoter near the RNAp binding site. CAP can apparently interact with RNAp to increase the rate of operon transcription about 50-fold. Positive control of the lac operon is illustrated in Figure 10.