Visualizing Epigenetics: A Review of Microscopy Techniques for Investigating DNA Methylation Patterns, Chromatin Structure, and Gene Expression

Abstract Microscopy approaches are frequently used to decipher the localization and quantify the abundance of biologically relevant molecular targets within single cells. Recent research has applied many optical imaging techniques to specifically visualize epigenetic modifications, the mechanisms by which organisms control gene expression in response to environmental factors. While many molecular and omics-based approaches are used to understand epigenetic mechanisms, imaging approaches provide spatial information that supplies greater context for discerning function. Thus, labeling approaches have been developed to quantify and visualize epigenetic targets using various fluorescence microscopy, electron microscopy, and super-resolution microscopy techniques. Here, we synthesize information about microscopy methods that enable visualization of epigenetic marks including DNA methylation, histone modifications, and localization of RNAs, which provide insights into mechanisms involved in chromatin remodeling and gene expression. The ability to determine how and where specific epigenetic marks manifest structurally and functionally in cells demonstrates the power of microscopy in aiding our understanding of epigenetic processes.