Epigenetics, memory, and inheritance

Dear Editor:

In a recent article, Rosales-Reynoso et al.¹ describe the known epigenetic mechanisms involved in memory formation and their role in the aetiopathogenesis of some hereditary neurological diseases. The authors suggest that multiple environmental stimuli lead to epigenetic modifications in the CNS that are critical to short- and long-term behavioural adaptation. According to the study, epigenetic modifications are involved in creating and maintaining behavioural memory on multiple levels. The article explains that CGG trinucleotide repeat expansion and increased DNA methylation in the promoter of the FMR1 gene prevent gene transcription and the production of messenger RNA and the FMR1 protein in such hereditary neurological diseases as fragile X syndrome.

In one of the first articles on the topic, published in 2010, we analysed the evidence that the number of epigenetic marks (DNA methylations) increases over an individual's life and that such methylations may be sufficiently stable to pass between generations.² More recent studies have supported this hypothesis, which has an enormous impact on our understanding of the aetiology of multifactorial diseases, hereditary diseases, and even processes which develop over an individual's entire lifetime, such as memory formation.³ The methylations occurring in brain neurons, which explain memory formation, are not hereditary since brain tissue is not involved in human reproduction. However, in line with our 2010 article,² we suggest that DNA methylations in reproductive cells formed in gonadal tissue, which are potentially inheritable and transmitted from generation to generation, may be involved in CGG trinucleotide repeat expansions and the absence of FMR1 protein expression. The accumulation of methylations in reproductive cells during an individual's lifetime may therefore have an impact on the genotype and phenotype of hereditary diseases in their offspring.

These epigenetic marks may be responsible for trinucleotide repeat expansions in various hereditary diseases; treating these disorders constitutes another challenge for medicine today.⁴ Much progress is being made in these lines of research in the hope that advancing our knowledge of epigenetics may lead to improvements in the treatment of genetic diseases and those involving environmental factors, as is the case with multifactorial diseases.⁵