MeCP2 (human recombinant; methyl binding domain aa 77-166)

DNA methylation occurs mainly at the 5’-position of cytosine rings (5-methylcytosine (5mC)). The 5mC bases are found largely in genomic regions with a high frequency of cytosines and guanines, called CpG islands. Methyl-CpG binding protein 2 (MeCP2) specifically binds to methylated promoters on CpG islands and mediates gene silencing by recruiting corepressor complexes.¹ The Methyl-CpG Binding Domain (MBD) protein family consists of five members: MeCP2, MBD1, MBD2, MBD3 and MBD4.^2,3,4 The sequence similarity between the MBD proteins is limited to the MBD domains.⁵ In vitro work suggests high affinity binding of MeCP2 is facilitated by DNA fragments containing A/T bases ([A/T]≥4) adjacent to the methyl-CpG.⁶ Mutations in the MeCP2 gene have been linked to the X-linked neurological disorder, Rett Syndrome.⁷

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1. Ho, K.L., McNae, I.W., Schmiedeberg, L., et al. MeCP2 binding to DNA depends upon hydration at methyl-CpG. Mol. Cell 29(4), 525-531 (2008).

2. Fatemi, M., and Wade, P.A. MBD family proteins: Reading the epigenetic code. J. Cell Sci. 119(Pt. 15), 3033-3037 (2006).

3. Dhasarathy, A., and Wade, P.A. The MBD protein family-reading an epigenetic mark? Mutat. Res. 647(1-2), 39-43 (2008).

4. Hendrich, B., and Bird, A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol. Cell. Biol. 18(11), 6538-6547 (1998).

5. Berger, J., and Bird, A. Role of MBD2 in gene regulation and tumorigenesis. Biochem. Soc. Trans. 33(Pt. 6), 1537-1540 (2005).

6. Klose, R.J., Sarraf, S.A., Schmiedeberg, L., et al. DNA binding selectivity of MeCP2 due to a requirement for A/T sequences adjacent to methyl-CpG. Mol. Cell 19(5), 667-678 (2005).

7. Zachariah, R.M., and Rastegar, M. Linking epigenetics to human disease and Rett Syndrome: The emerging novel and challenging concepts in MeCP2 research. Neural Plast. 415825 (2012).