TY - JOUR

T1 - Different Mechanisms Confer Gradual Control and Memory at Nutrient- and Stress-Regulated Genes in Yeast

AU - Rienzo, Alessandro

AU - Poveda-Huertes, Daniel

AU - Aydin, Selcan

AU - Buchler, Nicolas E

AU - Pascual-Ahuir, Amparo

AU - Proft, Markus

N1 - Copyright © 2015, American Society for Microbiology. All Rights Reserved.

PY - 2015/11

Y1 - 2015/11

N2 - Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.

AB - Cells respond to environmental stimuli by fine-tuned regulation of gene expression. Here we investigated the dose-dependent modulation of gene expression at high temporal resolution in response to nutrient and stress signals in yeast. The GAL1 activity in cell populations is modulated in a well-defined range of galactose concentrations, correlating with a dynamic change of histone remodeling and RNA polymerase II (RNAPII) association. This behavior is the result of a heterogeneous induction delay caused by decreasing inducer concentrations across the population. Chromatin remodeling appears to be the basis for the dynamic GAL1 expression, because mutants with impaired histone dynamics show severely truncated dose-response profiles. In contrast, the GRE2 promoter operates like a rapid off/on switch in response to increasing osmotic stress, with almost constant expression rates and exclusively temporal regulation of histone remodeling and RNAPII occupancy. The Gal3 inducer and the Hog1 mitogen-activated protein (MAP) kinase seem to determine the different dose-response strategies at the two promoters. Accordingly, GAL1 becomes highly sensitive and dose independent if previously stimulated because of residual Gal3 levels, whereas GRE2 expression diminishes upon repeated stimulation due to acquired stress resistance. Our analysis reveals important differences in the way dynamic signals create dose-sensitive gene expression outputs.

KW - Galactokinase/genetics

KW - Galactose/metabolism

KW - Gene Expression Regulation, Fungal

KW - Genes, Regulator

KW - Histones/genetics

KW - Mitogen-Activated Protein Kinases/metabolism

KW - Oxidoreductases/genetics

KW - RNA Polymerase II/metabolism

KW - Saccharomyces cerevisiae/cytology

KW - Saccharomyces cerevisiae Proteins/genetics

KW - Stress, Physiological

KW - Trans-Activators/metabolism

KW - Transcription Factors/metabolism

U2 - 10.1128/MCB.00729-15

DO - 10.1128/MCB.00729-15

M3 - Journal article

C2 - 26283730

VL - 35

SP - 3669

EP - 3683

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 21

ER -