Transcription-driven genome organization: a model for chromosome structure and the regulation of gene expression tested through simulations.

ABSTRACT: Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and topologically-associating domains (TADs), to contact domains stabilized by cohesin and CTCF. However, molecular mechanisms underlying this folding, and the way folding affects transcriptional activity, remain obscure. Here we review physical principles driving proteins bound to long polymers into clusters surrounded by loops, and present a parsimonious yet comprehensive model for the way the organization determines function. We argue that clusters of active RNA polymerases and their transcription factors are major architectural features; then, contact domains, TADs and compartments just reflect one or more loops and clusters. We suggest tethering a ge

SUBMITTER: Cook PR 

PROVIDER: S-EPMC6212781 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature