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Uncovering epigenetic landscape: a new path for biomarkers identification and drug development

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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.

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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

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 demethylase

MBDs:

Methyl-CpG binding domain family proteins

miRNAs:

MicroRNAs

ncDNA:

Non-coding DNA

ncRNAs:

Non-coding RNAs

NLS:

Nuclear localization signal

oxi-mCs:

Oxidized forms of 5-methylcytosine

PAD4:

Deaminase enzymes peptidyl arginine deaminase 4

PBD:

Proliferating cell nuclear antigen-binding

PD:

Passive dilution

PHD:

Polybromo homology

PRMTs:

Proteins arginine methyltransferases

PTMs:

Histone Post-translational Modifications

PWWP:

Tetrapeptide chromatin binding

RISC:

RNA-induced silencing complex

RNAi:

RNA interference

SAM:

S-Adenosyl-l-methionine

SAH:

S-Adenosyl-l-homocysteine

SIRTs:

Sirtuins

TDG:

Thymine DNA glycosylase protein

TETs:

Ten–eleven translocation methylcytosine dioxygenases

UHRF1:

Ubiquitin-like with plant homeodomain and RING finger domain 1 protein

ZBG:

Zinc-binding group

α-KG:

α-Ketoglutarate

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Acknowledgements

The authors thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Universidade Federal de Ouro Preto (UFOP) for PhD Scholarship of Daiane T. Oliveira.

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  1. Programa de Pós-graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil

    Daiane Teixeira de Oliveira & Renata Guerra-Sá

  2. Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil

    Renata Guerra-Sá

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de Oliveira, D.T., Guerra-Sá, R. Uncovering epigenetic landscape: a new path for biomarkers identification and drug development. Mol Biol Rep 47, 9097–9122 (2020). https://doi.org/10.1007/s11033-020-05916-3

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