Affiliation:
1. Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, Centre National de la Recherche Scientifique UMR5242, Université Claude Bernard-Lyon 1 ; 69364 Lyon , France
2. Indian Institute of Science Education and Research (IISER) Tirupati ; Tirupati 517507 Andhra Pradesh , India
Abstract
Abstract
Topologically Associating Domains (TADs) have been suggested to facilitate and constrain enhancer–promoter interactions. However, the role of TAD boundaries in effectively restricting these interactions remains unclear. Here, we show that a significant proportion of enhancer–promoter interactions are established across TAD boundaries in Drosophila embryos, but that developmental genes are strikingly enriched in intra- but not inter-TAD interactions. We pursued this observation using the twist locus, a master regulator of mesoderm development, and systematically relocated one of its enhancers to various genomic locations. While this developmental gene can establish inter-TAD interactions with its enhancer, the functionality of these interactions remains limited, highlighting the existence of topological constraints. Furthermore, contrary to intra-TAD interactions, the formation of inter-TAD enhancer–promoter interactions is not solely driven by genomic distance, with distal interactions sometimes favored over proximal ones. These observations suggest that other general mechanisms must exist to establish and maintain specific enhancer–promoter interactions across large distances.
Funder
Fondation pour la Recherche Médicale
European Research Council
Université Claude Bernard Lyon 1
Publisher
Oxford University Press (OUP)
Cited by
1 articles.
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