5-formylcytosine and Nervous-System-Diseases

DNA methylation has been studied comprehensively and linked to both normal neurodevelopment and neurological diseases. The recent identification of several new DNA modifications, including 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, has given us a new perspective on the previously observed plasticity in 5mC-dependent regulatory processes. Here, we review the latest research into these cytosine modifications, focusing mainly on their roles in neurodevelopment and diseases.

Topics: 5-Methylcytosine; Cytosine; DNA Methylation; DNA-Cytosine Methylases; Humans; Models, Molecular; Nervous System Diseases; Neurogenesis

Mounting evidence has recently underscored the importance of DNA methylation in normal brain functions. DNA methylation machineries are responsible for dynamic regulation of methylation patterns in discrete brain regions. In addition to methylation of cytosines in genomic DNA (5-methylcytosine; 5mC), other forms of modified cytosines, such as 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, can potentially act as epigenetic marks that regulate gene expression. Importantly, epigenetic modifications require cognate binding proteins to read and translate information into gene expression regulation. Abnormal or incorrect interpretation of DNA methylation patterns can cause devastating consequences, including mental illnesses and neurological disorders. Although DNA methylation was generally considered to be a stable epigenetic mark in post-mitotic cells, recent studies have revealed dynamic DNA modifications in neurons. Such reversibility of 5mC sheds light on potential mechanisms underlying some neurological disorders and suggests a new route to correct aberrant methylation patterns associated with these disorders.

Topics: 5-Methylcytosine; Brain; Cytosine; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation; Humans; Nervous System Diseases; Neurons