Quantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics

Virginia L Pimmett (1) , Matthieu Dejean (1) , Carola Fernandez (1) , Antonio Trullo (1) , Edouard Bertrand (2, 1) , Ovidiu Radulescu (3) , Mounia Lagha (1)

1 IGMM - Institut de Génétique Moléculaire de Montpellier
2 CNRS - Centre National de la Recherche Scientifique
3 LPHI - Laboratory of Pathogen Host Interactions [Montpellier]

Genes are expressed in stochastic transcriptional bursts linked to alternating active and inactive promoter states. A major challenge in transcription is understanding how promoter composition dictates bursting, particularly in multicellular organisms. We investigate two key Drosophila developmental promoter motifs, the TATA box (TATA) and the Initiator (INR). Using live imaging in Drosophila embryos and new computational methods, we demonstrate that bursting occurs on multiple timescales ranging from seconds to minutes. TATA-containing promoters and INR-containing promoters exhibit distinct dynamics, with one or two separate rate-limiting steps respectively. A TATA box is associated with long active states, high rates of polymerase initiation, and short-lived, infrequent inactive states. In contrast, the INR motif leads to two inactive states, one of which relates to promoter-proximal polymerase pausing. Surprisingly, the model suggests pausing is not obligatory, but occurs stochastically for a subset of polymerases. Overall, our results provide a rationale for promoter switching during zygotic genome activation.

Domaines: Sciences du Vivant [q-bio]

Virginia L Pimmett, Matthieu Dejean, Carola Fernandez, Antonio Trullo, Edouard Bertrand, et al.. Quantitative imaging of transcription in living Drosophila embryos reveals the impact of core promoter motifs on promoter state dynamics. Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-24461-6⟩. ⟨hal-03382887⟩