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

Single-molecule genomics (SMG) enables detailed, genome-wide analysis of regulatory mechanisms on individual DNA molecules, revealing complex interactions and heterogeneity.

• Why it matters: Understanding genome regulation at the single-molecule level fills a critical gap left by traditional methods, which cannot capture molecular heterogeneity and dynamic chromatin interactions, essential for insights into gene control.
• What they did: The authors present a practical guide and best practices for adopting SMG, highlighting its ability to profile regulatory factors, epigenetic modifications, and chromatin organization on single DNA molecules across the genome.
• The result: This approach enhances our capacity to study genome regulation, offering detailed insights into the co-occurrence and dynamics of regulatory events, thereby advancing functional genomics research.