Titre
Systematic screening of enhancer-blocking insulators in Drosophila identifies their DNA sequence determinants.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Tonelli, A.
Auteure/Auteur
Cousin, P.
Auteure/Auteur
Jankowski, A.
Auteure/Auteur
Wang, B.
Auteure/Auteur
Dorier, J.
Auteure/Auteur
Barraud, J.
Auteure/Auteur
Zunjarrao, S.
Auteure/Auteur
Gambetta, M.C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1878-1551
Statut éditorial
Publié
Date de publication
2025-02-24
Volume
60
Numéro
4
Première page
630
Dernière page/numéro d’article
645.e9
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Long-range transcriptional activation of gene promoters by abundant enhancers in animal genomes calls for mechanisms to limit inappropriate regulation. DNA elements called insulators serve this purpose by shielding promoters from an enhancer when interposed. Unlike promoters and enhancers, insulators have not been systematically characterized due to lacking high-throughput screening assays, and questions regarding how insulators are distributed and encoded in the genome remain. Here, we establish "insulator-seq" as a plasmid-based massively parallel reporter assay in Drosophila cultured cells to perform a systematic insulator screen of selected genomic loci. Screening developmental gene loci showed that not all insulator protein binding sites effectively block enhancer-promoter communication. Deep insulator mutagenesis identified sequences flexibly positioned around the CTCF insulator protein binding motif that are critical for functionality. The ability to screen millions of DNA sequences without positional effect has enabled functional mapping of insulators and provided further insights into the determinants of insulators.
PID Serval
serval:BIB_2A951E5FC6A3
PMID
Open Access
Oui
Date de création
2024-11-19T13:52:17.901Z
Date de création dans IRIS
2025-05-20T14:05:01Z
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Nom
39532105.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
6.47 MB
Format
Adobe PDF
PID Serval
serval:BIB_2A951E5FC6A3.P001
URN
urn:nbn:ch:serval-BIB_2A951E5FC6A38
Somme de contrôle
(MD5):ce65214fbcdf8869a1b9df5bee7a425f