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


RESULTS
In 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.


CONCLUSIONS
We 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.
Bauer
Denis C
DC
Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld 4072 Australia. d.bauer@uq.edu.au
Buske
Fabian A
FA
Bailey
Timothy L
TL
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D050437:Genes, Developmental; D008957:Models, Genetic; D012097:Repressor Proteins / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D029721:Drosophila Proteins; D012097:Repressor Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors