Enhancer cooperativity can compensate for loss of activity over large genomic distances

Henry F Thomas (Korresp. Autor*in), Songjie Feng, Felix Haslhofer, Marie Huber, María García Gallardo, Vincent Loubiere, Daria Vanina, Mattia Pitasi, Alexander Stark, Christa Buecker (Korresp. Autor*in)

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

Abstract

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 are not well understood. Here, we developed a synthetic platform in mouse embryonic stem cells that allows building complex regulatory landscapes from the bottom up. We tested the system by integrating individual enhancers at different distances and confirmed that the strength of an enhancer contributes to 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.

OriginalspracheEnglisch
Seiten (von - bis)362-375.e9
FachzeitschriftMolecular Cell
Jahrgang85
Ausgabenummer2
DOIs
PublikationsstatusVeröffentlicht - 16 Jan. 2025

ÖFOS 2012

  • 106023 Molekularbiologie

Fingerprint

Untersuchen Sie die Forschungsthemen von „Enhancer cooperativity can compensate for loss of activity over large genomic distances“. Zusammen bilden sie einen einzigartigen Fingerprint.

Zitationsweisen