Details

Autor(en) / Beteiligte

• Qi, Zhan
• Jung, Christophe
• Bandilla, Peter
• Ludwig, Claudia
• Heron, Mark
• Sophie Kiesel, Anja
• Museridze, Mariam
• Philippou‐Massier, Julia
• Nikolov, Miroslav
• Renna Max Schnepf, Alessio
• Unnerstall, Ulrich
• Ceolin, Stefano
• Mühlig, Bettina
• Gompel, Nicolas
• Soeding, Johannes
• Gaul, Ulrike

Titel

Large‐scale analysis of Drosophila core promoter function using synthetic promoters

Ist Teil von

• Molecular systems biology, 2022-02, Vol.18 (2), p.e9816-n/a

Ort / Verlag

Germany: EMBO Press

Erscheinungsjahr

2022

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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, we carried out a comprehensive structure–function analysis in Drosophila. First, we performed a genome‐wide bioinformatic analysis, providing an improved picture of the sequence motifs architecture. We 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. We 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. Synopsis A large‐scale structure‐function analysis of ~3,000 synthetic promoters reveals the sequence determinants of Drosophila core promoters. Mutational analysis using synthetic promoters reveals a strong impact of various types of mutations on the promoter activity. The linear combination of the individual motif features largely accounts for the combinatorial effects on core promoter activity. The analysis of the response to an external stimulus (hormone activation) shows a correlation between the hormone responsiveness and the core promoter architecture. A large‐scale structure‐function analysis of ~3,000 synthetic promoters reveals the sequence determinants of Drosophila core promoters.