Visualizing, quantifying and mapping chromatin remodelers at work with single-molecule and single-cell imaging

Abstract

Chromatin remodeling, carried out by four major subfamilies of ATP-dependent remodeler complexes across eukaryotes, alleviates the topological challenge posed by nucleosomes to regulate genome access. Recently, single-molecule and single-cell imaging techniques have been widely employed to probe this crucial process, both in vitro and in cellulo. Herein, we provide an integrated account of key recent efforts that leverage these approaches to visualize, quantify and map chromatin remodelers at work, elucidating diverse aspects of the remodeling process in both space and time, including molecular mechanisms of DNA wrapping/unwrapping, nucleosome translocation and histone exchange, dynamics of chromatin binding/target search and their intranuclear organization into hotspots or phase condensates, as well as functional coupling with transcription. The mechanistic insights and quantitative parameters revealed shed light on a multi-modal yet shared landscape for regulating remodeling across molecular and cellular scales, and pave the way for further interrogating the implications of its misregulation in disease contexts.