Contrasting regulatory landscapes determine the activation of a single gene in different developmental contexts

FRANKEL, NICOLÁS

Taller; V Taller de Biología Celular y del Desarrollo; 2022

The organization of regulatory information in animal genomes is largely unknown. Evolutionaryanalyses have estimated that the percentage of functionally relevant nucleotides in intergenic regionsof the D. melanogaster genome is ~60%. This estimation is difficult to reconcile with the idea thatenhancers are compact regulatory elements that generally encompass less than 1 kb. In this work, weapproach this apparent paradox through the functional dissection of the regulatory region of the geneshavenbaby (svb). Most of the ~90 kb of this large regulatory region is highly conserved in the genusDrosophila, though characterized enhancers occupy a small fraction of this non-coding region. Byanalyzing the regulation of svb in different contexts of D. melanogaster development, we show that theregulatory landscape of the svb locus in the abdominal pupal epidermis is remarkably different fromthat of the epidermis of the embryo. While svb activation in the epidermis of the embryo is achievedthrough compact and disperse enhancers, svb expression in the pupal epidermis is the result of theactivity of large regions with enhancer activity, which occupy most of the regulatory region of svb.These results suggest that evolutionary constraints on non-coding DNA of Drosophila might beexplained by the density of regulatory information