4.8 Article

Reading the unique DNA methylation landscape of the brain: Non-CpG methylation, hydroxymethylation, and MeCP2

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1411269112

Keywords

non-CpG methylation; hydroxymethylation; MeCP2; Rett syndrome

Funding

  1. Rett Syndrome Research Trust
  2. National Institutes of Health (NIH) [1R01NS048276]
  3. William Randolph Hearst fund
  4. NIH [T32GM007753]
  5. Howard Hughes Medical Institute Gilliam Fellowship

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DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.

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