Epigenetic and Epitranscriptomic Determinants of Host-Microbe Interactions

Dear Colleagues,

Humans interact with a myriad of microorganisms from environmental exposures and the microbiome. Many of these microbes are essential to human health, such as the heterogeneous gastrointestinal microbiome responsible for the digestion of nutrients, immune surveillance, and critical metabolites, while others pose threats as primary or opportunistic pathogens. While the molecular mechanisms of microbial pathogenesis have been studied for more than a century, we are only now beginning to appreciate how the diversity of bacteria, archaea, viruses, and fungi in the microbiome, which varies significantly among individuals due to diet, lifestyle and host genetics, determines human health and disease. Growing evidence links microbiome dysbiosis to various diseases, including cancer, due to a complex metabolic interplay between the microbes and the human host. For example, it is well established that normally commensal microbes can become pathogenic due to ill-defined mechanisms of immune dysfunction and microbiome imbalances. Similarly, host pathologies such as inflammatory bowel disease are known to alter the gut microbiome but with unknown causes and consequences.

All microbes and their human hosts share two features of molecular genetics with surprisingly strong links to health and disease: epigenetic and epitranscriptomic regulation of gene expression. While the Central Dogma defines the “what” of biology—that genes are transcribed into messenger RNAs that are translated into proteins—it says nothing about the “when” or “how much” of expressing 4000–5000 genes in bacteria or >20,000 genes in humans. Convergent technologies have revealed information-rich scheduling systems for gene expression involving the dozens of chemical modifications of DNA, RNA, and histone proteins in every cell—the epigenome and epitranscriptome. Many of the epigenome and epitranscriptome components have been known for more than 50 years, but their functions have only recently emerged. DNA modifications, such as 5-methyl-2’-deoxycytidine in humans, are now known to regulate gene expression at the transcription level, with microbes possessing a much larger diversity of DNA modifications also involved in antimicrobial defense. Epigenetic control of gene expression in eukaryotes is regulated in parallel by dozens of histone protein secondary modifications. Analogously, the epitranscriptome comprises >170 chemical modifications of all forms of RNA in all organisms, with roughly 50 RNA modifications in every organism functioning in part to regulate gene expression at the translation level.

This Special Issue of Epigenomes presents the most up-to-date overview of the role of epigenomes and epitranscriptomes in the interplay between microbes and humans in healthy homeostasis and disease. Among the many topics covered here, the articles address discoveries of epigenetic marks in bacteriophage and bacteria, comparative genomics of epigenome and epitranscriptome machinery, breakthroughs in understanding the epitranscriptome-linked metabolic interdependencies of microbes and humans, and convergent analytical and informatic technologies for discovering, quantifying and mapping DNA and RNA modifications. Through a collection of research articles, reviews, and perspectives, readers will gain insights into the latest advancements in the emerging field of epigenetic and epitransciptomic determinants of host–microbe interactions.

Dr. Mudasir Rashid
Dr. Manjula Das
Guest Editors

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