As someone with limited background in cell physiology and genomics, I found this descriptive article about The 4D Nucleome Project extremely helpful:
For example, this pithy pearl is mind-blowing for anyone old enough to remember when the newly described deoxyribonucleic acid was just starting to inspire ping-pong ball and
Tinker Toy models at elementary school science fairs:
Therefore, to determine how the genome operates, we need to understand not only the linear encoding of information along chromosomes, but also its 3-dimensional organization and its dynamics across time, i.e. the “4D nucleome”.
For a layperson like me, these are jaw-dropping advancements:
The spatial folding of chromosomes and their organization in the nucleus have profound impact on gene expression. For example, spatial proximity is necessary for enhancers to modulate transcription of target genes (e.g.5–7), and clustering of chromatin near the nuclear lamina is correlated with gene silencing and replication timing8,9. Meanwhile, genome-wide association studies have identified large numbers of disease-associated loci, and the majority of them are located in distal, potentially regulatory, noncoding regions (e.g.10).