In situ tools for chromatin structural epigenomics

Technological progress over the past 15 years has fueled an explosion in genome-wide chromatin profiling tools that take advantage of low-cost short-read sequencing technologies to map particular chromatin features. Here, we survey the recent development of epigenomic tools that provide precise positions of chromatin proteins genome-wide in intact cells or nuclei. Some profiling tools are based on tethering Micrococcal Nuclease to chromatin proteins of interest in situ, whereas others similarly tether Tn5 transposase to integrate DNA sequencing adapters (tagmentation) and so eliminate the need for library preparation. These in situ cleavage and tagmentation tools have gained in popularity over the past few years, with many protocol enhancements and adaptations for single-cell and spatial chromatin profiling. The application of experimental and computational tools to address problems in gene regulation, eukaryotic development, and human disease are helping to define the emerging field of chromatin structural epigenomics.