Optogenetic Control Reveals Differential Promoter Interpretation of Transcription Factor Nuclear Translocation Dynamics
| Autor: | Susan Chen, Andrew H. Ng, Lukasz J. Bugaj, Taylor H. Nguyen, R.A. Greenstein, Lauren T. Neves, Jacob Stewart-Ornstein, Hana El-Samad, Lindsey C. Osimiri, Michael Chevalier |
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| Rok vydání: | 2020 |
| Předmět: |
Histology
Saccharomyces cerevisiae Proteins Active Transport Cell Nucleus Gene Expression Chromosomal translocation Bioengineering Saccharomyces cerevisiae Optogenetics Article Pathology and Forensic Medicine Promoter Regions 03 medical and health sciences 0302 clinical medicine Genetic transcription factors Gene expression dynamic decoding medicine Genetics Differential expression Promoter Regions Genetic Gene Transcription factor 030304 developmental biology Cell Nucleus 0303 health sciences Chemistry Dynamics (mechanics) Promoter nucleo-cytoplasmic pulsing Cell Biology Phenotype Nuclear translocation Active Transport Cell biology DNA-Binding Proteins Protein Transport translocation dynamics medicine.anatomical_structure promoter interpretation Biochemistry and Cell Biology Nucleus 030217 neurology & neurosurgery Nuclear localization sequence Transcription Factors Biotechnology |
| Zdroj: | Cell systems, vol 11, iss 4 Cell systems |
| Popis: | SUMMARY Gene expression is thought to be affected not only by the concentration of transcription factors (TFs) but also the dynamics of their nuclear translocation. Testing this hypothesis requires direct control of TF dynamics. Here, we engineer CLASP, an optogenetic tool for rapid and tunable translocation of a TF of interest. Using CLASP fused to Crz1, we observe that, for the same integrated concentration of nuclear TF over time, changing input dynamics changes target gene expression: pulsatile inputs yield higher expression than continuous inputs, or vice versa, depending on the target gene. Computational modeling reveals that a dose-response saturating at low TF input can yield higher gene expression for pulsatile versus continuous input, and that multi-state promoter activation can yield the opposite behavior. Our integrated tool development and modeling approach characterize promoter responses to Crz1 nuclear translocation dynamics, extracting quantitative features that may help explain the differential expression of target genes. Graphical Abstract In Brief CLASP is a modular optogenetic strategy to control the nuclear localization of transcription factors (TFs) and elicit gene expression from their cognate promoters. CLASP control of Crz1 nuclear localization, coupled with computational modeling, revealed how promoters can differentially decode dynamic transcription factor signals. The integrated strategy of CLASP development and modeling presents a generalized approach to causally investigate the transcriptional consequences of dynamic TF nuclear shuttling. |
| Databáze: | OpenAIRE |
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