Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity

Julie Carnesecchi, Gianluca Sigismondo, Katrin Domsch, Clara Eva Paula Baader, Mahmoud-Reza Rafiee, Jeroen Krijgsveld and Ingrid Lohmann ()
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Julie Carnesecchi: Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and CellNetworks - Cluster of Excellence
Gianluca Sigismondo: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581
Katrin Domsch: Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and CellNetworks - Cluster of Excellence
Clara Eva Paula Baader: Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and CellNetworks - Cluster of Excellence
Mahmoud-Reza Rafiee: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581
Jeroen Krijgsveld: German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581
Ingrid Lohmann: Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology and CellNetworks - Cluster of Excellence

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Transcription factors (TFs) control cell fates by precisely orchestrating gene expression. However, how individual TFs promote transcriptional diversity remains unclear. Here, we use the Hox TF Ultrabithorax (Ubx) as a model to explore how a single TF specifies multiple cell types. Using proximity-dependent Biotin IDentification in Drosophila, we identify Ubx interactomes in three embryonic tissues. We find that Ubx interacts with largely non-overlapping sets of proteins with few having tissue-specific RNA expression. Instead most interactors are active in many cell types, controlling gene expression from chromatin regulation to the initiation of translation. Genetic interaction assays in vivo confirm that they act strictly lineage- and process-specific. Thus, functional specificity of Ubx seems to play out at several regulatory levels and to result from the controlled restriction of the interaction potential by the cellular environment. Thereby, it challenges long-standing assumptions such as differential RNA expression as determinant for protein complexes.

Date: 2020
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DOI: 10.1038/s41467-020-15223-x

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