Genome‐wide transcriptional plasticity underlies cellular adaptation to novel challenge

Citations Over TimeTop 10% of 2007 papers

Abstract

Cells adjust their transcriptional state to accommodate environmental and genetic perturbations. An open question is to what extent transcriptional response to perturbations has been specifically selected along evolution. To test the possibility that transcriptional reprogramming does not need to be 'pre-designed' to lead to an adaptive metabolic state on physiological timescales, we confronted yeast cells with a novel challenge they had not previously encountered. We rewired the genome by recruiting an essential gene, HIS3, from the histidine biosynthesis pathway to a foreign regulatory system, the GAL network responsible for galactose utilization. Switching medium to glucose in a chemostat caused repression of the essential gene and presented the cells with a severe challenge to which they adapted over approximately 10 generations. Using genome-wide expression arrays, we show here that a global transcriptional reprogramming (>1200 genes) underlies the adaptation. A large fraction of the responding genes is nonreproducible in repeated experiments. These results show that a nonspecific transcriptional response reflecting the natural plasticity of the regulatory network supports adaptation of cells to novel challenges.

Related Papers

• → Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks(2013)100 cited
• → Precision of tissue patterning is controlled by dynamical properties of gene regulatory networks(2021)74 cited
• → Identify gene expression pattern change at transcriptional and post-transcriptional levels(2019)22 cited
• → Partially observed bipartite network analysis to identify predictive connections in transcriptional regulatory networks(2011)6 cited
• → Exploring induced pluripotency in human fibroblasts via construction, validation, and application of a gene regulatory network(2019)2 cited