Epigenetics today and tomorrow

Abstract

Epigenetics is the science of the heritable properties of the organism that are not associated with changes in the DNA nucleotide sequence but can be indirectly encoded in the genome. The most well-known epigenetic mechanisms (signals) are enzymatic DNA methylation, the histone code (various enzymatic histone modifications including acetylation, methylation, phosphorylation, ubiquitination, etc.), and gene silencing mediated by small RNAs (miRNA, siRNA). All these processes are usually interconnected and even partially interchangeable. This is apparently required for the reliable implementation of epigenetic signaling. Anyway, these processes are closely associated with chromatin structural and functional organization. DNA methylation in plants and animals, performed by site-specific enzymes, cytosine DNA-methyltransferases, produces 5-methylcytosine (m5C) residues in DNA sequences such as CG, CNG, and CNN. Adenine DNA methylation also occurs in plants. The resulting m5C residues in DNA substantially affect the interaction of DNA with different proteins, including regulatory proteins. DNA methylation often prevents DNA binding to such proteins and inhibits gene transcription, but sometimes it is required for binding to other regulatory proteins. Specific m5CpG DNA-binding proteins were described. The binding of such proteins to DNA orchestrates the whole protein ensemble of the transcription machinery and induces its activity. Thus, DNA methylation can serve as a signal of positive and negative control for gene activities. DNA methylation in eukaryotes is species- and tissue-specific. It is regulated by hormones, changes with age, and is one of the mechanisms controlling cellular and sex differentiation. DNA methylation controls all genetic processes: DNA replication, repair, recombination, transcription, etc. Distortions in DNA methylation and other epigenetic signals cause premature aging, cancer, diabetes, asthma, severe mental dysfunctions, etc. Changes in the DNA methylation profile accompany carcinogenesis and are a reliable diagnostic marker of various types of cancer even at the early stages of tumorigenesis. Epigenetic parameters are very important for understanding the somaclonal variation mechanisms; characterization of clones and cell cultures, including stem cells at various differentiation stages; and determination of their differentiation directions. Directed change in the DNA methylation profile is an efficient biotechnological tool for activation of transcription of seed storage protein genes in cereals and it is used, in particular, for an inheritable increase in protein content in wheat grain. The inhibitor of DNA methylation with 5-azacytidine is used for treatment of skin cancer. Various regulators of enzymatic modifications of histones are already used in clinical practice for the treatment of some human and animal diseases. The use of specific small RNAs in the therapy of cancer and other diseases appears to be particularly promising, especially in connection with directed inhibition of transcription of the genes responsible for cell malignization and metastasis. The therapeutic effect of many small biologically active peptides can be largely determined by their action at the epigenetic level. Thus, the phenotype is the product of combined realization of the genome and epigenome. In this regard, P. Medawar’s well-known expression “genetics supposes, epigenetics disposes” sounds quite correct and very impressive. Epigenetics is a quickly developing and very promising science of the 21st century that is already ingrained in biotechnologies, medicine, and agriculture.