Neuronal DNA methylation and hydroxymethylation system (5mC/5hmC-CpG)

Methylated (5mC) and hydroxymethylated (5hmC) CpG dinucleotides are fundamental epigenetic marks within neuronal chromatin that orchestrate the complex gene expression patterns required for brain development and function (Kriaucionis & Heintz, 2009). In neurons, 5hmC is exceptionally abundant compared to other tissues and is typically associated with transcriptionally active loci and synaptic plasticity (Mellén et al., 2012). These modifications are interpreted by a suite of cofactors, most notably Methyl-CpG-binding protein 2 (MeCP2), which can act as a transcriptional repressor or activator depending on the specific modification and genomic context (Amir et al., 1999). The balance between these marks is maintained by the opposing actions of DNA methyltransferases (DNMTs) and Ten-eleven translocation (TET) enzymes (Tahiliani et al., 2009). Dysregulation of this epigenetic system is a hallmark of various neurological conditions, including Rett syndrome, which is caused by mutations in the MeCP2 reader protein, and neurodegenerative diseases like Alzheimer's (Colquitt et al., 2013). Pharmacological strategies often target the enzymes responsible for writing or erasing these marks, such as DNMT inhibitors, to restore normal transcriptional profiles (Szyf, 2009).

Other names

5-methylcytosine and 5-hydroxymethylcytosine in neuronal chromatinNeuronal epigenetic landscape5mC/5hmC-CpG complexNeuronal methylome

Inhibition of DNA methyltransferases (DNMTs) to reduce 5mC levels, or modulation of Ten-eleven translocation (TET) enzymes to promote the conversion of 5mC to 5hmC.