Gene regulation is offering a new class of targets that operate on a higher level than DNA sequences and epigenetic markers: 3-D genomic structures. While strategies to drug the 3-D genome are still in their infancy, the growing accessibility of mapping technologies is paving the way for translation in cancer and developmental disorders.
DNA has long been known to wrap around histone protein complexes in stretches of about 150 bases, forming chromatin that is made more or less accessible by epigenetic modifications, such as lysine and methyl tags. However, less is understood about the higher order chromatin loops and clusters, known as topologically associating domains (TADs), which involve DNA stretches on the order of tens of kilobases to several megabases.
In the last five years, advances in sequencing- and imaging-based methods to characterize these structures have catalyzed research studies dissecting their role in controlling gene expression.
The question is whether better understanding of the 3-D genome will yield therapies that correct dysfunctional gene expression in disease.
“The factors that govern chromatin topology are likely to represent powerful targets for