Technological advances in probing 4D genome organization

The last two decades of work on chromosome conformation in eukaryotic nuclei have revealed a complex and highly regu-lated hierarchy of architectural features, from self-associating domains and compartmental interactions to locus-specific loops. Recent findings have shown that these structures are dynamic and heterogeneous, with emerging insights into the factors that shape them and implications for the control of transcription and other nuclear processes. Here, we review the latest advances in the DNA sequencing-and microscopy-based technologies for probing these features in space and time (4D) and discuss how they have been combined with complementary approaches such as genetic perturbations, protein and RNA measurements, and modeling to gain mechanistic insights about genome regulation across space and time.

Automated summary

The last two decades have seen significant progress in understanding the complex hierarchy of chromosome conformation in eukaryotic nuclei. Recent findings have revealed the dynamic and heterogeneous nature of these structures and their implications for genome regulation. This review discusses the latest advances in technology, such as DNA sequencing and microscopy, for studying these features in space and time, and how they have been combined with other approaches to gain mechanistic insights.