DNA Methylation in Memory Formation

Abstract

The establishment of synaptic plasticity and long-term memory requires lasting cellular and molecular modifications that, as a whole, must endure despite the rapid turnover of their constituent parts. Such a molecular feat must be mediated by a stable, self-perpetuating, cellular information storage mechanism. DNA methylation, being the archetypal cellular information storage mechanism, has been heavily implicated as being necessary for stable activity-dependent transcriptional alterations within the central nervous system (CNS). This review details the foundational discoveries from both gene-targeted, as well as whole-genome sequencing, studies that have successfully brought DNA methylation to our attention as a chief regulator of activity- and experience-dependent transcriptional alterations within the CNS. We present a hypothetical framework with which the disparate experimental findings dealing with distinct manipulations of the DNA methylation, and their effect on memory, might be resolved while taking into account the unique impact activity-dependent alterations in DNA methylation potentially have on both memory promoting and memory-suppressing gene expression. And last, we discuss potential avenues for future inquiry into the role of DNA methylation during remote memory formation.

Genome-wide DNA methylation profiling identifies convergent molecular signatures associated with idiopathic and syndromic forms of autism in post-mortem human brain tissue

“…There is increasing evidence to support a role for non-sequence-based genomic variation in the etiology of neurodevelopmental phenotypes including ASD 13 . The epigenetic regulation of gene expression in the central nervous system is involved in modulating many core neurobiological and cognitive processes including neurogenesis 14,15 , neuronal plasticity 16 and memory formation 17,18 , and is known to be highly dynamic during human brain development 19 . The dysregulation of epigenetic mechanisms underlies the symptoms of Rett syndrome and Fragile X syndrome, two disorders with considerable phenotypic overlap with ASD [20][21][22] , and epigenetic variation has been recently associated with several neurodevelopmental phenotypes including ASD 12,[23][24][25][26][27][28][29][30][31] .…”

Non-Coding and Loss-of-Function Coding Variants in TET2 are Associated with Multiple Neurodegenerative Diseases

“…This finding is important for two main reasons. First, TET2 plays an important role in the conversion of methylation to 5-hydroxymethylation, implicating dysfunction in a pathway known to be critical during aging 50 and learning and memory 51 in age-associated diseases like LOAD and FTD. Second, it is striking that the effect sizes in both coding and non-coding variant enrichments were comparable.…”

Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy

“…DNA methylation patterns can be made by laboratory techniques, such as sodium bisulfite sequencing, methyl-sensitive polymerase chain reaction (PCR) and DNA methylation array microchips (Shen & Waterland, 2007; Figure 2). donor (Heyward & Sweatt, 2015). DNMT1 is an essential enzyme responsible for the preservation of existing methylation throughout the DNA replication process.…”