DNA Methylation of the Dopamine Transporter DAT1 Gene—Bliss Seekers in the Light of Epigenetics

Abstract

DNA methylation (leading to gene silencing) is one of the best-studied epigenetic mechanisms. It is also essential in regulating the dynamics of dopamine release in the synaptic cleft. This regulation relates to the expression of the dopamine transporter gene (DAT1). We examined 137 people addicted to nicotine, 274 addicted subjects, 105 sports subjects and 290 people from the control group. After applying the Bonferroni correction, our results show that as many as 24 out of 33 examined CpG islands had statistically significantly higher methylation in the nicotine-dependent subjects and athletes groups compared to the control group. Analysis of total DAT1 methylation revealed a statistically significant increase in the number of total methylated CpG islands in addicted subjects (40.94%), nicotine-dependent subjects (62.84%) and sports subjects (65.71%) compared to controls (42.36%). The analysis of the methylation status of individual CpG sites revealed a new direction of research on the biological aspects of regulating dopamine release in people addicted to nicotine, people practicing sports and people addicted to psychoactive substances.

N6‐methyladenosine modification of RNA controls dopamine synthesis to influence labour division in ants

“…Polyphenism, an important characteristic of social insects, is also reversible, implying an important role for RNA epigenetics in regulating labour division in social insects. Although the mechanism by which DNA methylation or histone modification influences labour division through the dopamine pathway has not been reported in social insects, DNA methylation has been shown to be critical for regulating the dynamics of dopamine release in the synaptic gap by suppressing the expression level of DAT in humans (Chmielowiec et al., 2023). Histone modifications induce phencyclidine to activate Dop1 in humans (Aoyama et al., 2014).…”

A Relevant Role for Dopamine Transporter Gene in Highly Sensitive Persons under Stressful Conditions: Focus on Genetic and Epigenetic Regulation

“…In par�cular, we report in highly sensi�ve subjects with higher PSS scores when compared to those less stressed, an increase in DNA methyla�on at one specific CpG site (number 5) at gene 5'UTR, and it is known that this epigene�c mechanism is associated with a reduc�on in gene expression since prevents the binding of transcrip�on factors to DNA (Robertson, 2005). DNA methyla�on of the human DAT1 gene has been extensively inves�gated since 80% of its promoter is formed by GCs sequences and it has mul�ple CpG islands (Bannon et al, 2001;Shumay et al, 2010), and altera�ons in gene epigene�c mark have been reported in different phenotypes pathological and not (Adriani et al, 2018;Annunzi et al, 2023;Chmielowiec et al, 2023;Song et al, 2014), showing at specific CpG sites both reduc�ons, as well as increases, as we here report (Chmielowiec et al, 2023;Hillemacher et al, 2009;Rubino et al, 2020). In par�cular, the transi�on from an�-correla�on in low-risk towards direct correla�on in high-risk subjects, as far as CpGs 3 (or 6) and 5 are concerned, was similarly found in our previous studies on internet addic�on (Annunzi et al, 2023;Nardi et al, 2020).…”