Project title: Linking location and action: mechanisms of Hox protein motif usage.
Type of rotation: M1 (2 months) or M2 (6 months)
Supervisors: Corinne Maurel-Zaffran and Yacine Graba
Project summary
Shared protein domains or motifs are usually seen as serving similar functions. While studying Drosophila Hox proteins, evolutionary conserved transcription factors with key function in development, evolution and pathology, we found that protein motifs in two phylogenetically closely related sister transcription factors (Ubx and AbdA) that share multiple functions are distinctly used for achieving them (unpublished). This indicates that not only motif presence but also motif usage is central to changes/evolution of protein activity. The project aims at uncovering the molecular and cellular bases for Ubx and AbdA distinct motif usage. The core hypothesis of the project is that distinct motif usage results from sequestration of Ubx and AbdA in distinct nuclear foci. This is supported by the observation that Ubx and AbdA form about 100 foci within a nucleus and that these foci are largely non-overlapping. Work will use high resolution microscopy to comparatively monitor Ubx and AbdA sub-nuclear distribution and study its dependency on sequences that distinguish Ubx from AbdA (using Ubx/AbdA chimeras), and correlate foci distribution with motif usage.
Recent team publications related to the project
1) Poliacikova G, Maurel-Zaffran C, Graba Y, Saurin AJ. Hox Proteins in the Regulation of Muscle Development. Front Cell Dev Biol. 2021 Oct 18;9:731996.
2) Wilmerding A, Rinaldi L, Caruso N, Lo Re L, Bonzom E, Saurin AJ, Graba Y, Delfini M-C. HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1. Development. 2021 Jan 20:dev.195404.
3) Rinaldi L, Saurin AJ, Graba Y. Fattening the perspective of Hox protein specificity through SLiMming. Int J Dev Biol. 2018;62(11-12):755-766.
4) Saurin AJ, Delfini MC, Maurel-Zaffran C, Graba Y. The Generic Facet of Hox Protein Function. Trends Genet. 2018 Dec;34(12):941-953.
5) Zouaz A, Auradkar A, Delfini MC, Macchi M, Barthez M, Ela Akoa S, Bastianelli L, Xie G, Deng WM, Levine SS, Graba Y, Saurin AJ. The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription. EMBO J. 2017 Oct 2;36(19):2887-2906.