Dynamics and biological relevance of epigenetic N6-methyladenine DNA modification in eukaryotic cells

DNA methylation represents a major type of DNA modifications that play key roles in diverse biological processes. With the recent development of highly selective and sensitive bioanalytical techniques, N-6-methyladenine (6mA) has been characterized as an important internal DNA modification dynamically occurring in multiple eukaryotes including humans. Increasing evidence has indicated that 6mA may act as a novel epigenetic modification involved in regulation of development, stress response and diseases such as cancer and neurodegenerative disorders. We review herein the recent advances in the detection and functional studies of 6mA modification, with special emphasis on its biological consequences and human health relevance as well as its dynamic regulation by various types of methyltransferases, demethylases and 6mA-binding proteins. It can be envisaged that further chemical and biological studies of 6mA modification will lead to a better understanding about its potentially important roles in normal and pathological biological processes. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

DNA methylation is a key type of DNA modification that plays important roles in biological processes. Recent studies have identified N-6-methyladenine (6mA) as an internal DNA modification that occurs dynamically in various eukaryotes, including humans. Increasing evidence suggests that 6mA may act as a novel epigenetic modification involved in the regulation of development, stress response, and diseases such as cancer and neurodegenerative disorders. This review summarizes the recent advances in detecting and studying the functional effects of 6mA modification, focusing on its biological consequences, relevance to human health, and dynamic regulation by methyltransferases, demethylases, and 6mA-binding proteins. Further research on the chemical and biological aspects of 6mA modification is expected to provide a better understanding of its potentially important roles in normal and pathological biological processes.