A revised model for promoter competition based on multi-way chromatin interactions

Autor: C L Harrold, Hughes, A M Oudelaar, Douglas R. Higgs, Jelena Telenius, Hanssen Llp.
Jazyk: angličtina
Rok vydání: 2019
Předmět:
DOI: 10.1101/612275
Popis: Specific communication between gene promoters and enhancers is critical for accurate regulation of gene expression. However, it remains unclear how specific interactions between multiple regulatory elements and genes contained within a single chromatin domain are coordinated. Recent technological advances allow for the investigation of multi-way chromatin interactions at single alleles in individual nuclei. This can provide insights into how multiple regulatory elements cooperate or compete for transcriptional activation. We have used these techniques in a mouse model in which the α-globin domain is extended to include several additional genes. This allows us to determine how the interactions of the α-globin super-enhancer are distributed between multiple promoters in a single domain. Our data show that gene promoters do not form mutually exclusive interactions with the super-enhancer, but all interact simultaneously in a single complex. These finding show that promoters within the same domain do not structurally compete for interactions with enhancers, but form a regulatory hub structure, consistent with the recent model of transcriptional activation in phase-separated nuclear condensates.
Databáze: OpenAIRE