期刊
CELL SYSTEMS
卷 11, 期 4, 页码 336-+出版社
CELL PRESS
DOI: 10.1016/j.cels.2020.08.009
关键词
-
资金
- NIH [R01GM119033]
- National Science Foundation (NSF) Graduate Research Fellowship (GRF)
- National Defense Science & Engineering Graduate (NDSEG) Fellowship
- Paul and Daisy Soros Fellowship for New Americans
- National Institute for General Medical Sciences (NIGMS) Initiative for Maximizing Student Development (IMSD) Fellowship
- ARCS Foundation Scholarship
- Hooper Graduate Fellowship
- Arnold O. Beckman Postdoctoral Fellowship
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据