Dynamic control of gene regulatory logic by seemingly redundant transcription factors

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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.

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Zohreh AkhavanAghdam

Section of Molecular Biology, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
Joydeb Sinha

Section of Molecular Biology, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
Omar P Tabbaa

Section of Molecular Biology, University of California, San Diego, La Jolla, United States

Competing interests
The authors declare that no competing interests exist.
Nan Hao

Section of Molecular Biology, University of California, San Diego, La Jolla, United States

For correspondence
nhao@ucsd.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2857-4789

Funding

National Institutes of Health (R01 GM111458)

Nan Hao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.