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RESEARCH PRODUCT

Epigenetic Mechanisms as Key Regulators in Disease

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Epigenetics is a rapidly growing field of research which studies the changes in the gene expression that do not involve changes in the nucleotide sequence. The cellular metabolism is directly connected to epigenetic regulation through the inflow of different metabolites such as S-adenosylmethionine, acetyl-CoA, and α-ketoglutarate among others, which serve as substrates or cofactors for chromatin-modifying enzymes. These metabolites define how our lifestyle (i.e., nutrition, physical activity, and other healthy behaviors) acts on gene expression by epigenetic mechanisms. Therefore, proper coordination between components of the epigenetic machineries is essential for the correct control of the epigenome, otherwise mutations in epigenetic enzymes and/or in epigenetic readers can translate into diseases. Some rare diseases, which will be the focus of the present chapter, such as immunodeficiency, centromeric region instability, and facial anomalies syndrome, Rett syndrome, Rubinstein–Taybi syndrome, and Weaver syndrome 2 originated from mutations in DNMT3B, in methyl CpG-binding protein 2, and in histone posttranslational modifiers, respectively. Thus, alterations in the epigenetic machineries deregulate different epigenetic substrates, which in turn might be implemented as clinical epigenetic biomarkers for diagnosis, prognosis, and monitoring a wide variety of pathological conditions.