The core promoter plays a central role in setting metazoan gene expression levels, but how exactly it “computes” expression remains poorly understood. To dissect its function, a team of the former Gaul group in collaboration with Johannes Söding and Nicolas Gompel carried out a comprehensive structure–function analysis in Drosophila. First, they performed a genome-wide bioinformatic analysis, providing an improved picture of the sequence motifs architecture. They then measured synthetic promoters’ activities of ~3,000 mutational variants with and without an external stimulus (hormonal activation), at large scale and with high accuracy using robotics and a dual luciferase reporter assay.
They observed a strong impact on activity of the different types of mutations, including knockout of individual sequence motifs and motif combinations, variations of motif strength, nucleosome positioning, and flanking sequences. A linear combination of the individual motif features largely accounts for the combinatorial effects on core promoter activity. These findings shed new light on the quantitative assessment of gene expression in metazoans.
The authors dedicate this publication to the memory of Prof. Ulrike Gaul who deceased after a long illness during the review of the manuscript.
Large-scale analysis of Drosophila core promoter function using synthetic promoters.
Qi Z, Jung C, Bandilla P, Ludwig C, Heron M, Sophie Kiesel A, Museridze M, Philippou-Massier J, Nikolov M, Renna Max Schnepf A, Unnerstall U, Ceolin S, Mühlig B, Gompel N, Soeding J, Gaul U.
Mol Syst Biol. 2022 Feb;18(2):e9816.