Coupling of DNA Replication and Negative Feedback Controls Gene Expression for Cell-Fate Decisions
Qiuyan Shao,
Michael G. Cortes,
Jimmy T. Trinh,
Jingwen Guan,
Gábor Balázsi,
Lanying Zeng
Affiliations
Qiuyan Shao
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA; Center for Phage Technology, Texas A&M University, College Station, TX 77843, USA
Michael G. Cortes
The Louis and Beatrice Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, USA; Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA
Jimmy T. Trinh
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA; Center for Phage Technology, Texas A&M University, College Station, TX 77843, USA
Jingwen Guan
Center for Phage Technology, Texas A&M University, College Station, TX 77843, USA; Molecular and Environmental Plant Science, Texas A&M University, College Station, TX 77843, USA
Gábor Balázsi
The Louis and Beatrice Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, NY, USA; Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA; Corresponding author
Lanying Zeng
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA; Center for Phage Technology, Texas A&M University, College Station, TX 77843, USA; Molecular and Environmental Plant Science, Texas A&M University, College Station, TX 77843, USA; Corresponding author
Summary: Cellular decision-making arises from the expression of genes along a regulatory cascade, which leads to a choice between distinct phenotypic states. DNA dosage variations, often introduced by replication, can significantly affect gene expression to ultimately bias decision outcomes. The bacteriophage lambda system has long served as a paradigm for cell-fate determination, yet the effect of DNA replication remains largely unknown. Here, through single-cell studies and mathematical modeling we show that DNA replication drastically boosts cI expression to allow lysogenic commitment by providing more templates. Conversely, expression of CII, the upstream regulator of cI, is surprisingly robust to DNA replication due to the negative autoregulation of the Cro repressor. Our study exemplifies how living organisms can not only utilize DNA replication for gene expression control but also implement mechanisms such as negative feedback to allow the expression of certain genes to be robust to dosage changes resulting from DNA replication. : Gene Network; Microbial Genomics; Bioinformatics; Mathematical Biosciences Subject Areas: Gene Network, Microbial Genomics, Bioinformatics, Mathematical Biosciences
