Edited by Jun-An Chen and Yi-Ching Wang
A thematic series in Journal of Biomedical Science.
In 1942, British developmental biologist Conrad Waddington coined the term “epigenetics”. Later, he published a paper in the journal Evolution (Waddington, 1956) in which he demonstrated inheritance in a population of a characteristic acquired in response to an environmental stimulus. Such “epigenetic” evolution typically relates to functionally relevant changes to the genome that do not involve an alteration in the DNA sequence. Since then, impacts of epigenetic regulation have been unveiled in almost all aspects of biology, including cell differentiation, embryonic development, aging and degeneration. Recently, the new term of “epitranscriptome,” has been applied to biochemical modifications of RNA (the transcriptome), and thus is analogous to epigenetics. How such RNA modifications affect gene expression and whether “epigenetic” and “epitranscriptomic” crosstalk is critical in coordinating embryonic development and disease progression remain to be established.
This collection of reviews on epigenetic and epitranscriptomic regulation explores how modifications of DNA, RNA, and histones contribute to development and disease. Specifically, Kim et al. discuss the multifaceted roles of lysine-specific demethylase 1A (LSD1) in cancers, such as via hypoxia, the epithelial-to-mesenchymal transition, stemness versus differentiation of cancer stem cells, as well as anti-tumor immunity. Nepali & Liou further summarize the development pipeline for LSD1 inhibitors and provide an update on almost all FDA-approved epigenetic drugs and the epigenetic inhibitors undergoing clinical-stage investigations for various cancers. Importantly, though aberrant epigenetic changes may be linked to genome instability in disease contexts, detailed mechanisms have yet to be defined. Herein, Hsu et al. provide an overview of how transposable elements and their crosstalk with epigenetic marks might participate in disease surveillance. Apart from transposable element-mediated genome integrity, Hsu et al. further propose a canonical role for epigenetic marks in histone dynamics during replication stress and highlight recent advances in characterizing mechanisms protecting replication forks that are mediated by histone marks. Finally, Yen & Chen explore progress in studying the functions of N6-methyladenosine (m6A), the most prevalent RNA modification mark, during neural development and degeneration. Given that epigenetics and epitranscriptomics represent emerging topics in life science research, we hope that this thematic series will pave the way for the readership of the Journal of Biomedical Science to advance the frontiers of this exciting field.