Abstract
Experience-dependent plasticity is the ability of brain circuits to undergo molecular, structural and functional changes as a function of neural activity. Neural activity continuously shapes our brain during all the stages of our life, from infancy through adulthood and beyond. Epigenetic modifications of histone proteins and DNA seem to be a leading molecular mechanism to modulate the transcriptional changes underlying the fine-tuning of synaptic connections and circuitry rewiring during activity-dependent plasticity. The recent discovery that cytosine methylation is an epigenetic mark particularly dynamic in brain cells has strongly increased the interest of neuroscientists in understanding the role of covalent modifications of DNA in activity-induced remodeling of neuronal circuits. Here, we provide an overview of the role of DNA methylation and hydroxylmethylation in brain plasticity both during adulthood, with emphasis on learning and memory related processes, and during postnatal development, focusing specifically on experience-dependent plasticity in the visual cortex.
Highlights
Phenotype is the result of the dynamic and continuous interaction between genes and environment
DNA methylation is a covalent modification that occurs on cytosine mostly located in CG dinucleotides (CpG) by means of a reaction catalysed by a family of enzymes called DNA methyltransferases (DNMT)
These results reveal that visual deprivation has opposite effects on DNA methylation and hydroxyl methylation on specific genomic regions and suggest that these modifications could be brought about by the visual regulation of DNMT, GADD45 and APOBEC-3 expression and possibly their DNA binding
Summary
Phenotype is the result of the dynamic and continuous interaction between genes and environment. Brain cells depend on complex and highly regulated mechanisms to appropriately activate or silence gene programs in response to inputs from the environment. These events are controlled by activity-dependent signaling pathways that mediate gene expression by modifying the activity, localization, and/or expression of transcriptional-regulatory enzymes in combination with alterations in chromatin structure in the nucleus (McClung and Nestler, 2008). The concept of an ‘‘epigenetic landscape’’ might be applied to differentiated cells like neurons that are continuously targeted by different inputs and choose their fate (to make or not a synaptic contact, to spike or not, to wire in a particular circuit) in accordance to the predominance of specific environmental stimuli that remodel the chromatin structure to activate or silence gene expression. Due to important discoveries in the last few years, in our review, we are focusing on covalent DNA modifications especially methylation and hydroxylmethylation involved in experience-dependent brain plasticity
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