Dual-functioning transcription factors in the developmental gene network of Drosophila melanogaster

Abstract

BackgroundQuantitative models for transcriptional regulation have shown great promise for advancing our understanding of the biological mechanisms underlying gene regulation. However, all of the models to date assume a transcription factor (TF) to have either activating or repressing function towards all the genes it is regulating.ResultsIn this paper we demonstrate, on the example of the developmental gene network in D. melanogaster, that the data-fit can be improved by up to 40% if the model is allowing certain TFs to have dual function, that is, acting as activator for some genes and as repressor for others. We demonstrate that the improvement is not due to additional flexibility in the model but rather derived from the data itself. We also found no evidence for the involvement of other known site-specific TFs in regulating this network. Finally, we propose SUMOylation as a candidate biological mechanism allowing TFs to switch their role when a small ubiquitin-like modifier (SUMO) is covalently attached to the TF. We strengthen this hypothesis by demonstrating that the TFs predicted to have dual function also contain the known SUMO consensus motif, while TFs predicted to have only one role lack this motif.ConclusionsWe argue that a SUMOylation-dependent mechanism allowing TFs to have dual function represents a promising area for further research and might be another step towards uncovering the biological mechanisms underlying transcriptional regulation.

Dissection of thousands of cell type-specific enhancers identifies dinucleotide repeat motifs as general enhancer features

“…4D). For the second one, the activity was enhanced in S2 cells, presumably because the mutations created another functional motif or because the CA DRM can exert both activating and repressing functions as is also known for other motifs and TFs (Bauer et al 2010).…”

ISMARA: automated modeling of genomic signals as a democracy of regulatory motifs

“…Second, the approach currently assumes that a given TF acts either mainly as an activator or mainly as a repressor, whereas it is clear that some TFs can act as an activator on some targets and as a repressor on others. Indeed, it has been recently shown (Bauer et al 2010) that allowing such dual function of TFs can significantly increase correlation between model predictions and measurement. Explicitly considering higher-order constella- (Bulyk 2006) and the decreasing cost in ChIP-seq experiments, regulatory motifs for a rapidly increasing number of additional mammalian TFs have recently become available.…”

Ehrlichia chaffeensis TRP32 Is a Nucleomodulin That Directly Regulates Expression of Host Genes Governing Differentiation and Proliferation

“…Dualfunction transcription factors can be regulated by several factors, including variations in the motif they bind, posttranslational modifications of the transcription factor, interaction with different transcription coregulators, or the general transcriptional milieu (i.e., cell cycle, cell type, cell activation status) (45)(46)(47). Posttranslational modification of TRP32 may play a role in regulating TRP32 transcription factor function.…”