Human chromosome.Hans RisGenome sequencing projects have provided rich troves of information about stretches of DNA that regulate gene expression, as well as how different genetic sequences contribute to health and disease. But these studies misses a key element of the genome—its spatial organization—which has long been recognized as an important regulator of gene expression. Regulatory elements often lie thousands of base pairs away from their target genes, and recent technological advances are allowing scientists to begin examining how distant chromosome locations interact inside a nucleus. The creation and function of 3-D genome organization, some say, is the next frontier of genetics.
Genome spatial organization is critical for gene regulation, explained Job Dekker, a molecular geneticist at the University of Massachusetts Medical School, and “everything else chromosomes do involves three dimensions,” as well. Chromosomes have to replicate, separate properly during division, and change shape during the cell cycle—all without tangling. The genome is “rebuilt entirely after cell division,” Dekker said.
The mechanisms for such delicate orchestration have remained unclear, however. About 10 years ago—just as the human genome project was completing its first draft sequence—Dekker pioneered a new technique, called chromosome conformation capture (C3) that allowed researchers to get a glimpse of how chromosomes are arranged relative to each other in the nucleus. The technique relies on the physical cross-linking of chromosomal regions that lie in ...
