Abstract
Precise genetic and epigenetic spatiotemporal regulation of gene expression is critical for proper brain development, function and circuitry formation in the mammalian central nervous system. Neuronal differentiation processes are tightly regulated by epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodelers and non-coding RNAs. Dysregulation of any of these pathways is detrimental to normal neuronal development and functions, which can result in devastating neuropsychiatric disorders, such as depression, schizophrenia and autism spectrum disorders. In this review, we focus on the current understanding of epigenetic regulations in brain development and functions, as well as their implications in neuropsychiatric disorders.
Highlights
The concept of epigenetics was first proposed in 1939 by Conrad Waddington to describe early embryonic development (Waddington, 1939)
5hmC can be converted to 5-hydroxymethyluracil (5hmU) via the activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing catalytic polypeptides (APOBEC) enzymes (Bhutani et al, 2011). All three of these derivatives (5fC, 5caC, and 5hmU) can be cleaved by thymine-DNA glycosylase (TDG), which excises the modified cytosine base allowing for the base excision repair (BER) pathway to return it to an unmodified cytosine base (Bhutani et al, 2011; He et al, 2011)
In mice that have experienced chronic social defeat stress and in postmortem brains from humans with clinical depression, HDAC2 protein is reduced in the nucleus accumbens (NAc; a brain region associated with reward) (Covington et al, 2009)
Summary
Karolinska Institutet (KI), Sweden Malav Suchin Trivedi, Northeastern University, United States. Specialty section: This article was submitted to Epigenomics and Epigenetics, a section of the journal Frontiers in Genetics. Precise genetic and epigenetic spatiotemporal regulation of gene expression is critical for proper brain development, function and circuitry formation in the mammalian central nervous system. Neuronal differentiation processes are tightly regulated by epigenetic mechanisms including DNA methylation, histone modifications, chromatin remodelers and non-coding RNAs. Dysregulation of any of these pathways is detrimental to normal neuronal development and functions, which can result in devastating neuropsychiatric disorders, such as depression, schizophrenia and autism spectrum disorders. We focus on the current understanding of epigenetic regulations in brain development and functions, as well as their implications in neuropsychiatric disorders
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