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; increasing levels dramatically simplifies networks as more transcription units are pressed into use. Consequently, results from GWAS can be reconciled with those involving overexpression. We apply this pan-genomic model to predict patterns of transcriptional activity in whole human chromosomes, and, as an example, the effects of the deletion causing the diGeorge syndrome.
Regional specialization in human nuclei: visualization of discrete sites of transcription by RNA polymerase III
A conserved organization of transcription during embryonic stem cell differentiation and in cells with high C value.
Transcriptional gene network inference from a massive dataset elucidates transcriptome organization and gene function
Nonspecific bridging-induced attraction drives clustering of DNA-binding proteins and genome organization
Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder
Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains
Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters
Endothelial cell differentiation is encompassed by changes in long range interactions between inactive chromatin regions
Live-cell analysis of endogenous GFP-RPB1 uncovers rapid turnover of initiating and promoter-paused RNA Polymerase II
Topological and statistical analyses of gene regulatory networks reveal unifying yet quantitatively different emergent properties
22q11 Deletion Syndrome
22q11.2 deletion syndrome, also known as DiGeorge syndrome, is a congenital disorder caused by a partial deletion of chromosome 22. Symptoms include heart defects, poor immune system function, a cleft palate, complications related to low levels of calcium in the blood, and delayed development. Discover the latest research on this disease here.