Uncovering epigenetic landscape: a new path for biomarkers identification and drug development
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REVIEW
Uncovering epigenetic landscape: a new path for biomarkers identification and drug development Daiane Teixeira de Oliveira1 · Renata Guerra‑Sá1,2 Received: 29 June 2020 / Accepted: 10 October 2020 © Springer Nature B.V. 2020
Abstract Scientific advances in recent decades have revealed an incredible degree of plasticity in gene expression in response to various environmental, nutritional, physiological, pathological, and behavioral conditions. Epigenetics emerges in this sense, as the link between the internal (genetic) and external (environmental) factors underlying the expression of the phenotype. Methylation of DNA and histone post-translationa modifications are canonical epigenetic events. Additionally, noncoding RNAs molecules (microRNAs and lncRNAs) have also been proposed as another layer of epigenetic regulation. Together, these events are responsible for regulating gene expression throughout life, controlling cellular fate in both normal and pathological development. Despite being a relatively recent science, epigenetics has been arousing the interest of researchers from different segments of the life sciences and the general public. This review highlights the recent advances in the characterization of the epigenetic events and points promising use of these brands for the diagnosis, prognosis, and therapy of diseases. We also present several classes of epigenetic modifying compounds with therapeutic applications (so-call epidrugs) and their current status in clinical trials and approved by the FDA. In summary, hopefully, we provide the reader with theoretical bases for a better understanding of the epigenetic mechanisms and of the promising application of these marks and events in the medical clinic. Keywords DNA Methylation · Histone Post-translational Modifications · Non-coding RNAs · Biomarkers · Epidrugs · Clinical Trials Abbreviations 2HG 2-Hydroxyglutarate 5-caC 5-Carboxylcytosine 5-fC 5-Formylcytosine 5-hmC 5-Hydroxymethylcytosine 5-hmU 5-Hydroxymethyluracil 5-mC 5-Methylcytosine Ago Argonaute AR Active restoration ASO Oligonucleotides antisense ATRX Cytosine-rich zinc finger DNA binding BER Base excision repair DNMTi DNA methyltransferase inhibitors * Daiane Teixeira de Oliveira [email protected] 1
Programa de Pós‑graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil
Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil
2
DNMTs DNA methyltransferases DOT1L Disruptor of telomeric silencing-1-like FDA Food and Drug Administration HATs Histone acetyltransferases HDACi Histone deacetylase inhibitors HDACs Histone deacetylases HDMs Histone demethylases HKMTs Histone lysine methyltransferases HMTi Histone methyltransferases inhibitors HMTs Histone methyltransferases IDH Isocitrate dehydrogenase JmjC Jumonji C JMJD6 Jumonji domain-containing protein 6 KDMTs Histone lysine demethylase lncRNAs Long non-coding RNAs LSD Lysine specific demethyl
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