Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs

Jeremy Dufourt (1) , Antonio Trullo (1) , Jennifer Hunter (1) , Carola Fernandez (1) , Jorge Lazaro (1) , Matthieu Dejean (1) , Lucas Morales (1) , Saida Nait-Amer (1) , Katharine Schulz (2) , Melissa M Harrison (2) , Cyril Favard (3) , Ovidiu Radulescu (4) , Mounia Lagha (1)

1 IGMM - Institut de Génétique Moléculaire de Montpellier
2 Department of Biomolecular Chemistry [Madison, WI, USA]
3 IRIM - Institut de Recherche en Infectiologie de Montpellier
4 DIMNP - Dynamique des interactions membranaires normales et pathologiques

Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence. However, the impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains unclear. Here we employ quantitative live imaging methods and mathematical modeling to test the effect of the pioneer factor Zelda on transcriptional dynamics and memory in Drosophila embryos. We demonstrate that increasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past. Despite its known pioneering activities, we show that Zelda does not remain detectably associated with mitotic chromosomes and is neither necessary nor sufficient to foster memory. We further reveal that Zelda forms sub-nuclear dynamic hubs where Zelda binding events are transient. We propose that Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps.

Domaines: Biophysique; Embryologie et organogenèse

Jeremy Dufourt, Antonio Trullo, Jennifer Hunter, Carola Fernandez, Jorge Lazaro, et al.. Temporal control of gene expression by the pioneer factor Zelda through transient interactions in hubs. Nature Communications, 2018, 9 (1), pp.821 - 841. ⟨10.1038/s41467-018-07613-z⟩. ⟨hal-02323402⟩