RT Journal Article
SR Electronic
T1 Enhancer cooperativity can compensate for loss of activity over large genomic distances
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.12.06.570399
DO 10.1101/2023.12.06.570399
A1 Thomas, Henry
A1 Feng, Songjie
A1 Huber, Marie
A1 Loubiere, Vincent
A1 Vanina, Daria
A1 Pitasi, Mattia
A1 Stark, Alexander
A1 Buecker, Christa
YR 2023
UL http://biorxiv.org/content/early/2023/12/07/2023.12.06.570399.abstract
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.