Complex small-world regulatory networks emerge from the 3D organisation of the human genome.

ABSTRACT: The discovery that overexpressing one or a few critical transcription factors can switch cell state suggests that gene regulatory networks are relatively simple. In contrast, genome-wide association studies (GWAS) point to complex phenotypes being determined by hundreds of loci that rarely encode transcription factors and which individually have small effects. Here, we use computer simulations and a simple fitting-free polymer model of chromosomes to show that spatial correlations arising from 3D genome organisation naturally lead to stochastic and bursty transcription as well as complex small-world regulatory networks (where the transcriptional activity of each genomic region subtly affects almost all others). These effects require factors to be present at sub-saturating levels; increasin

SUBMITTER: Brackley CA 

PROVIDER: S-EPMC8486811 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature