Dynamics of Viral and Host 3D Genome Structure upon Infection
Meyer J. Friedman, Haram Lee, Young‐Chan Kwon, Soohwan Oh
Abstract
Distal cis-regulatory enhancers control appropriate transcription of genes in eukaryotes through their interaction with proximal cis-regulatory promoters. These DNA regulatory elements, which exhibit distinctive epigenetic features, can be separated by tens to hundreds of kilobases (kb) and contain binding sequences for specific transcription factors (TFs) that drive gene expression in part by recruiting co-factors endowed with various enzymatic activities responsible for altering the epigenetic landscape. Advances in the gene regulation field have revealed that 3D chromatin (re-)organization plays an important role in bringing enhancers in close proximity to their target promoters The structure of the 3D genome largely relies on architectural proteins such as CTCF, cohesin, and YY1 [2]. These architectural proteins contribute not only to topologically associated domains (TADs), which are demarcated by boundaries, but also to smaller chromatin loops within TADs, such as enhancer-promoter (E-P) interactions. In addition to the characteristic epigenetic properties of enhancers and promoters, CTCF/cohesin effects on 3D chromatin organization are a key determinant of E-P interaction specificity and thus spatiotemporal regulation of gene expression Intriguingly, depletion of host architectural proteins, including CTCF or cohesin, also affects reactivation and replication of many viruses (Table These results imply that the viral life cycle can be regulated by chromosome architecture and further suggest viral mechanisms involving genome organization during infection.