Lineage-specific Protein Interactomes of the Hox Transcription Factor Ubx revealed by Close-Proximity Protein Biotinylation

ABSTRACT: Cell type diversity is controlled by transcription factors (TFs), which regulate specific yet flexible gene expression programs depending on the cellular environment. However, how sets of TFs work together to promote such diversity with high precision is still unknown. We used the Hox TF Ultrabithorax (Ubx) as a model because of its essential functions in multiple cell types. Assuming that functional diversity emerges from specifc protein interactions in different cell types, we explored Ubx protein interactomes in three different tissue lineages in vivo. Using proximity dependent Biotin IDentification (BioID) in Drosophila embryos, we find that Ubx interacts with largely non-overlapping sets of proteins in each tissue lineage. Intriguingly, this specificity does not primarily result from Ubx binding to proteins with lineage-restricted functions. Instead, Ubx interacts in a lineage-specific manner with ubiquitously expressed subunits of proteins complexes controlling general aspects of gene expression, like chromatin remodelling or RNA processing. Thus, our work reveals that cell type-specific protein interaction networks not necessarily involve cell type-specific partners and that the function of key TFs may extend to the control over the entire realm of gene expression, including splicing and translation. These findings challenge two central dogmas in cell lineage specification, namely the strong reliance on differential RNA expression as a measure for specificity determinants and the enhancer-centric approach to understand gene regulation.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Embryo

SUBMITTER: Gianluca Sigismondo  

LAB HEAD: Ingrid Lohmann

PROVIDER: PXD014481 | Pride | 2020-04-22

REPOSITORIES: Pride