title: Dissecting dynamic genetic variation that controls temporal gene response in yeast.
abstract: Inter-individual variation in regulatory circuits controlling gene expression is a powerful source of functional information. The study of associations among genetic variants and gene expression provides important insights about cell circuitry but cannot specify whether and when potential variants dynamically alter their genetic effect during the course of response. Here we develop a computational procedure that captures temporal changes in genetic effects, and apply it to analyze transcription during inhibition of the TOR signaling pathway in segregating yeast cells. We found a high-order coordination of gene modules: sets of genes co-associated with the same genetic variant and sharing a common temporal genetic effect pattern. The temporal genetic effects of some modules represented a single state-transitioning pattern; for example, at 10-30 minutes following stimulation, genetic effects in the phosphate utilization module attained a characteristic transition to a new steady state. In contrast, another module showed an impulse pattern of genetic effects; for example, in the poor nitrogen sources utilization module, a spike up of a genetic effect at 10-20 minutes following stimulation reflected inter-individual variation in the timing (rather than magnitude) of response. Our analysis suggests that the same mechanism typically leads to both inter-individual variation and the temporal genetic effect pattern in a module. Our methodology provides a quantitative genetic approach to studying the molecular mechanisms that shape dynamic changes in transcriptional responses.
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Brodt
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Botzman
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Irit
authors.initials: I
authors.lastname: Gat-Viks
mesh_terms: D000465:Algorithms; D000935:Antifungal Agents / Q000494:pharmacology; D019295:Computational Biology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D015003:Yeasts / Q000235:genetics*
chemical_list: D000935:Antifungal Agents; D020123:Sirolimus