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Review
. 2014 Dec 5:8:397.
doi: 10.3389/fnins.2014.00397. eCollection 2014.

The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases

Sahar Al-Mahdawi  1 , Sara Anjomani Virmouni  1 , Mark A Pook  1
Affiliations
Review

The emerging role of 5-hydroxymethylcytosine in neurodegenerative diseases

Sahar Al-Mahdawi et al. Front Neurosci. .

Abstract

DNA methylation primarily occurs within human cells as a 5-methylcytosine (5mC) modification of the cytosine bases in CpG dinucleotides. 5mC has proven to be an important epigenetic mark that is involved in the control of gene transcription for processes such as development and differentiation. However, recent studies have identified an alternative modification, 5-hydroxymethylcytosine (5hmC), which is formed by oxidation of 5mC by ten-eleven translocation (TET) enzymes. The overall levels of 5hmC in the mammalian genome are approximately 10% of 5mC levels, although higher levels have been detected in tissues of the central nervous system (CNS). The functions of 5hmC are not yet fully known, but evidence suggests that 5hmC may be both an intermediate product during the removal of 5mC by passive or active demethylation processes and also an epigenetic modification in its own right, regulating chromatin or transcriptional factors involved in processes such as neurodevelopment or environmental stress response. This review highlights our current understanding of the role that 5hmC plays in neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia (FRDA), Huntington's disease (HD), and Parkinson's disease (PD).

Keywords: 5-hydroxymethylcytosine; Alzheimer's disease; Friedreich ataxia; Huntington's disease; Parkinson's disease; amyotrophic lateral sclerosis; fragile X-associated tremor/ataxia syndrome.

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Figures

Figure 1
Figure 1
Functions of 5hmC. 5hmC has several different functions that impact upon gene transcription: (1) acting as an intermediate in passive DNA demethylation due to poor binding between 5hmC and UHRF1, the partner of DNMT1; (2) acting as an intermediate in TET/TDG/BER-based active DNA methylation; (3) altering the ratio of 5mC-binding proteins (5mC-BPs) to 5hmC-binding proteins (5hmC-BPs) that impair or activate gene transcription.
See this image and copyright information in PMC

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