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

Area of Science:

• Molecular Biology
• Epigenetics
• Cell Biology

Background:

• Chromatin remodeling is essential for regulating genome access by overcoming nucleosome-imposed topological challenges.
• ATP-dependent remodeler complexes play a crucial role in this process across eukaryotes.
• Understanding the dynamics and mechanisms of chromatin remodelers is vital for comprehending gene regulation.

Purpose of the Study:

• To provide an integrated overview of recent advancements in visualizing and quantifying chromatin remodeler activity.
• To elucidate the spatial and temporal aspects of chromatin remodeling processes.
• To explore the functional coupling of chromatin remodelers with transcription and their role in disease.

Main Methods:

• Application of single-molecule and single-cell imaging techniques, both in vitro and in cellulo.
• Quantitative analysis of chromatin remodeler dynamics, binding, and target search.
• Mapping the intranuclear organization of remodelers, including hotspots and phase condensates.

Main Results:

• Visualization and quantification of molecular mechanisms like DNA wrapping/unwrapping, nucleosome translocation, and histone exchange.
• Detailed insights into the dynamics of chromatin binding and target search by remodelers.
• Characterization of intranuclear organization into hotspots and phase condensates, and coupling with transcription.

Conclusions:

• Recent imaging techniques provide unprecedented mechanistic insights into chromatin remodeling across molecular and cellular scales.
• Quantitative parameters reveal a multi-modal regulatory landscape for chromatin remodelers.
• Further research into misregulation of chromatin remodeling is crucial for understanding disease contexts.