Epigenetic Regulation of Autophagy

Abstract

Epigenetics refers to reversible and hereditary changes in gene expression without alterations in DNA sequences, such as DNA methylation, histone modification and chromatin remodelling. It was first proposed by Waddington in the book Introduction to Modern Genetics in 1939. Autophagy includes at least four processes: autophagy induction, autophagosome formation, autophagosome fusion with lysosomes and lysosomal degradation of cytoplasmic components. The whole process is complex and dynamic, and involves at least 30 autophagy-related proteins. This degradative machinery is regulated by multiple signal molecules. Autophagy was once considered to be a cytoplasmic event; however, in recent years, emerging evidence suggests that nuclear components (transcription factors, histone modification, microRNAs, etc.) also play an important role in autophagy regulation (Baek and Kim 2017). Among them, epigenetic regulation of autophagy has gained much attention. The epigenetic machinery can not only modify autophagy-related genes but also affect some signal molecule genes that regulate autophagy, thus impacting their transcription and subsequent autophagy. This chapter focuses on the role and recent progress in autophagy regulation by DNA methylation and histone modifications. The role of non-coding RNAs such as microRNA in autophagy regulation will be covered in other chapters.