A practical guide to studying genome function using single-molecule genomics.

Single-molecule genomics (SMG) enables genome-wide profiling of regulatory factors on individual DNA molecules, revealing molecular heterogeneity and co-occurring regulatory events.

• Why it matters: Understanding the mechanisms that regulate the genome requires tools that can measure complex, dynamic interactions at the single-molecule level, which conventional methods cannot fully capture.
• What they did: The authors provide a practical guide and outline best practices for adopting SMG, emphasizing its ability to quantify epigenetic modifications, transcription factor binding, and chromatin organization.
• The result: SMG offers a unique platform to study chromatin interaction dynamics and how regulatory events combine to control genome activity, advancing insights into genome regulation mechanisms.