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The effects of these metabolic factors and their metabolites can impact gene expression by binding to transcription factors as well as by modifying chromatin structure and function ( In the common and chronic alcohol use disorder (AUD) the multiple exposure to ethanol produces an overall reduced anxiety which may be linked to opening of chromatin by increased histone acetylation, increased cAMP-response element binding protein (CREB) levels, and histone deacetylase (HDAC) inhibition ( Similarly, in the heroin abuse disorder methylation levels of CpG sites HTR1B_07 and HTR1B_26 and the promoter region of the HTR1B gene were hypermethylated in heroin abusers compared to healthy controls ( The enzymes involved in epigenetic modifications of the DNA as well as the histone methylation/acetylation are reliant on specific micronutrient cofactors (Figure 3) and their activity can be directly impacted by the levels of these cofactors like nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD) as well as metabolic compounds like L-carnitine, Q10, etc
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