Complex small-world regulatory networks emerge from the 3D organisation of the human genome.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
27
05
2021
accepted:
30
08
2021
entrez:
2
10
2021
pubmed:
3
10
2021
medline:
25
2
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34599163
doi: 10.1038/s41467-021-25875-y
pii: 10.1038/s41467-021-25875-y
pmc: PMC8486811
doi:
Substances chimiques
Chromatin
0
Polymers
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5756Informations de copyright
© 2021. The Author(s).
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