Genetic modes of epigenetic modification and its research progress

Abstract

It is known that genomic information is not only contained in the DNA sequence, but also in varieties of genetic effects, namely epigenetics. Epigenetics is defined as stable inheritance without changes in DNA sequence, which mainly focuses on the modification regulations, including DNA methylation, histone modification, non-coding RNA, X chromatin inactivation, gene imprinting, chromatin remodeling and so on. In the past few decades, epigenetics has made a dramatic advance, and quantities of mechanisms underlie the epigenetic phenomena have been discovered. Among these, DNA methylation and histone modifications are two most important aspects in epigenetic phenomena. The major DNA methylation and demethylation happen on cytosines of the CpG dinucleotide in mammals. In this process, DNA methyltransferase (DNMT) family proteins and ten-eleven translocation methylcytosine dioxygenase (TET) family proteins cooperate and achieve the both methylation and demethylation progress. Several covalent modifications of histones can alter the nucleosome conformation by changing the electrostatic charge of it, which include histone methylation, acetylation, phosphorylation and ubiquitination. In histone modification procedure, a set of enzymes are involved, Polycomb group (PcG) and Trithorax group (TrxG) functioning in histone methylation, for instance. These modifications fit together and lead to distinct state of chromatin accessibility, resulting in either gene expression or repression. Long-range chromatin interactions organize chromatin into transcriptionally permissive or prohibitive, thereby regulating gene expression. Non-coding RNAs also play critical roles in gene expression process through interacts directly with DNA, RNA, proteins. The epigenetic mechanisms mentioned above work cooperatively in gene expression regulation, which is essential for normal development and survival. Moreover, the epigenetic information can be inherited from parents to offsprings. Previous studies have shed light on the mechanisms underlying the epigenetic inheritance, but many questions remain unanswered. For example, DNA methylation and histone modifications can be passed through a series of enzymatic reactions with the join of other biological molecules. However, in what way does the machinery conduct the epigenetic information passage between generations is not well understood. In addition, the environment can certainly influence gene expression in an epigenetic manner. Particular environmental factor may interact with the regulators in epigenetic modification and consequently change the phenotype. Recent studies showed abnormal epigenetic states commonly exist in diseases, which imply a correlation between epigenetic modifications and diseases. Furthermore, mutations in epigenetic regulators always cause dysregulation of epigenetic modifications and then diseases. Thus, those epigenetic regulators can be potential targets in treatment of diseases. In this review, we focused on the mechanisms of epigenetic inheritance reported in recent years. Meanwhile, we proposed some questions that researchers met during their work and drew a blueprint for the study in the future.