Epigenetics is the study of heritable, chemical changes to DNA that do not alter the DNA sequence. Epitranscriptomics is based on the exact same idea but focuses on the biochemical changes at the RNA level. Often dynamic, both epigenetic and epitranscriptomic changes are dictated by external stimuli or the physiological or pathological conditions of a cell. These changes regulate downstream gene expression and biological processes. These rapidly evolving areas of research highlight a previously unappreciated layer of gene regulation, which was entirely unknown a decade or two ago.
Epigenetic modifications include reversible changes in DNA bases and histone. Though all four DNA bases can be chemically modified, some of the most prevalent DNA modifications involve 5-methylcytosine (5mC) and its oxidative derivatives. In addition to these base modifications, histone modifications, such as methylation, acetylation, phosphorylation, and ubiquitination also belong to epigenetic memory. Both DNA and histone modifications alter DNA’s access to the transcriptional machinery that influence transcriptional activity and ensure proper regulation of gene expression and thereby cell processes.
Epitranscriptomic modifications include more than 175 types of methylation and hypermethylations discovered so far in RNA molecules including mRNA, rRNA, tRNA, sncRNAs (miRNAs, piRNAs), cirCRNAs, and lncRNAs. Of the base modifications identified to date, N6-methyladenosine (m6A) is the most abundant and important epitranscriptomic player in RNA localization, stability, and translation efficiency. m6A accounts for 0.1–0.4 percent of the total adenosine in cellular mRNA, approximately two–three sites per transcript, which are critical for RNAs to facilitate their full functions. Dedicated writer, eraser, and reader molecules regulate dynamic processes or epitranscriptomic modifications and subsequent RNA fates.
Recent advances in high-throughput sequencing techniques have enabled systematic epigenome/ epitranscriptome-wide mapping of markers for human diseases. Emerging discoveries have highlighted links between aberrantly regulated gene and protein expression at the epigenomic/epitranscriptomic level and human pathologies like cancers, neurological disorders, heart diseases, hematological diseases, kidney diseases, etc. Recent discoveries have made significant progress in our understanding of epigenetically and epitranscriptomically regulated disease pathogenesis and, going forward, may lead to new therapeutic applications.