PT  - JOURNAL ARTICLE
AU  - A. Marieke Oudelaar
AU  - Caroline L. Harrold
AU  - Lars L. P. Hanssen
AU  - Jelena M. Telenius
AU  - Douglas R. Higgs
AU  - Jim R. Hughes
TI  - A revised model for promoter competition based on multi-way chromatin interactions
AID  - 10.1101/612275
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 612275
4099  - http://biorxiv.org/content/early/2019/04/17/612275.short
4100  - http://biorxiv.org/content/early/2019/04/17/612275.full
AB  - 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.