Abstract
Many transcription factors co-express with their homologs to regulate identical target genes, however the advantages of such redundancies remain elusive. Using single-cell imaging and microfluidics, we study the yeast general stress response transcription factor Msn2 and its seemingly redundant homolog Msn4. We find that gene regulation by these two factors is analogous to logic gate systems. Target genes with fast activation kinetics can be fully induced by either factor, behaving as an 'OR' gate. In contrast, target genes with slow activation kinetics behave as an 'AND' gate, requiring distinct contributions from both factors, upon transient stimulation. Furthermore, such genes become an 'OR' gate when the input duration is prolonged, suggesting that the logic gate scheme is not static but rather dependent on the input dynamics. Therefore, Msn2 and Msn4 enable a time-based mode of combinatorial gene regulation that might be applicable to homologous transcription factors in other organisms.
Highlights
Homologous transcription factors (TFs) often co-exist in eukaryotic cells, resulting in seemingly redundant regulation of their target genes
We have previously demonstrated that Msn2/4 target genes differ significantly in their promoter activation kinetics, which dramatically influences their responses to dynamic inputs (Hao and O’Shea, 2012)
Msn4 is required for the induction of target genes with slow promoter kinetics
Summary
Homologous transcription factors (TFs) often co-exist in eukaryotic cells, resulting in seemingly redundant regulation of their target genes. Recent studies suggest that some closely related TF homologs or isoforms, which regulate a shared set of target genes, might have diverged expression patterns, dynamic responses or gene regulatory functions. Computational and Systems Biology eLife digest Cells respond to environmental signals by activating proteins called transcription factors These bind to the DNA that is stored in the cell nucleus and turn on specific genes to make gene products. Two homologous transcription factors called Msn and Msn are found in baker’s yeast These transcription factors respond to a wide variety of environmental stresses by moving rapidly into the nucleus, where they remain for a short time to turn on hundreds of target genes that are needed for the cell to survive. Our work reveals that the seemingly redundant TF Msn has a distinct gene regulatory role from its homolog Msn and enables diversified gene expression responses within a cell population, which might be beneficial for survival under rapidly changing environments
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