PT  - JOURNAL ARTICLE
AU  - Thomas, Henry
AU  - Feng, Songjie
AU  - Huber, Marie
AU  - Loubiere, Vincent
AU  - Vanina, Daria
AU  - Pitasi, Mattia
AU  - Stark, Alexander
AU  - Buecker, Christa
TI  - Enhancer cooperativity can compensate for loss of activity over large genomic distances
AID  - 10.1101/2023.12.06.570399
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.12.06.570399
4099  - http://biorxiv.org/content/early/2023/12/07/2023.12.06.570399.short
4100  - http://biorxiv.org/content/early/2023/12/07/2023.12.06.570399.full
AB  - Enhancers are short DNA sequences that activate their target promoter from a distance; however, increasing the genomic distance between the enhancer and the promoter decreases expression levels. Many genes are controlled by combinations of multiple enhancers, yet the interaction and cooperation of individual enhancer elements is not well understood. Here, we developed a novel synthetic platform that allows building complex regulatory landscapes from the bottom up. We tested the system by integrating individual enhancers at different distances and revealed that the strength of an enhancer determines how strongly it is affected by increased genomic distance. Furthermore, synergy between two enhancer elements depends on the distance at which the two elements are integrated: introducing a weak enhancer between a strong enhancer and the promoter strongly increases reporter gene expression, allowing enhancers to activate from increased genomic distances.Competing Interest StatementThe authors have declared no competing interest.