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. Author manuscript; available in PMC: 2016 Jun 4.
Published in final edited form as: Annu Rev Genomics Hum Genet. 2015 Jun 4;16:55–77. doi: 10.1146/annurev-genom-090413-025437

Figure 7.

Figure 7

mCH in Rett syndrome. (a) As the brain matures, the abundances of mCH (blue) and MeCP2 (red) increase dramatically, while the abundance of mCG (brown) remains stable. (b) The binding affinity of MeCP2 to mCH (blue), mCG (brown), and unmethylated DNA (black) varies under different MeCP2 protein concentrations. The scales of panels a and b are schematic. (c) In immature brain, MeCP2 binds only to mCG sites owing to both a low mCH level and a low MeCP2 concentration. In mature brain, the increased mCH level and MeCP2 concentration enable the binding of (extra) MeCP2 at mCH sites in the bodies of genes that typically have a length greater than 100 kb and are enriched for neurological function (27). Based on this model, only in mature brain does disrupting MeCP2 function or concentration result in misregulation of long genes that is severe enough to cause a neurological disorder. The prototype of this model was proposed by Chen et al. (15), and the gene length feature of MeCP2-regulated genes was found by Gabel et al. (27). Abbreviations: mCG, CG methylation; mCH, non-CG methylation; MeCP2, methyl CpG binding protein 2. Adapted from figure 6 of Reference 15.