Dynamic Control of Gene Regulatory Logic by Seemingly Redundant Transcription Factors

Elife. 2016 Sep 30;5:e18458. doi: 10.7554/eLife.18458.

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.

Keywords: S. cerevisiae; computational biology; gene regulatory logic; homologous transcription factors; microfluidics; quantitative microscopy; signal dynamics; single-cell analysis; systems biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal*
  • Microfluidics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Single-Cell Analysis
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • DNA-Binding Proteins
  • MSN2 protein, S cerevisiae
  • MSN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors