Cells show a remarkable regulatory flexibility that allows them to thrive under different external conditions and to survive harsh situations. The ability to constantly sense and adapt to environmental changes is important for all organisms to maintain cellular functions (home- ostasis), but is especially acute for plants and microor- ganisms; their sessile lifestyle leave them more exposed to the environment than animals. Modulation of gene expression has a central role in cellular adaptation to short- or long-term environmental changes, with exten- sive regulation occurring at both the transcriptional and post-transcriptional level. Signal-transduction pathways can translate extracellular signals into specific intracel- lular responses, including the launch of alternative gene expression programmes to cope with new conditions. In addition to these ‘hard-wired’ responses, gene expres- sion networks show considerable plasticity to adapt to a wide range of challenges, including those not encoun- tered during evolutionary history (for example, ectopic gene expression). The application of genome-wide approaches is now providing a global view on gene expression responses to many different stress conditions, leading to exciting recent advances in our understanding of the cellular strategies that are used to stay in tune with environ- mental conditions. Many of these concepts have been developed in microorganisms, most notably yeast cells, which finely balance energy-efficient growth with the ability to rapidly adapt to sudden external challenges, and which provide ideal models to study gene expres- sion under tightly controlled conditions. Research in yeast and in other organisms is uncovering conserved principles for regulatory strategies in response to chang- ing environments. This Review will highlight some of the emerging principles underlying gene expression responses to environmental factors. The emphasis will be on transcriptional mechanisms, which have been most intensely studied for technical and histori- cal reasons, and for which several recent papers have greatly advanced our understanding. The details of regulatory pathways or specific cellular responses to different stresses have been reviewed elsewhere 1–4 . We focus on the general principles by which cells are able to adjust their gene expression programmes to respond to changing environments, both in the short-term and over evolutionary timescales. Emerging data reveal that cells finely balance the expression of stress-related and growth-related genes, which are antagonistic pro- grammes distinguished by distinct regulatory mecha- nisms. Stress-related genes generally contain TATA boxes, a promoter element that seems to promote both short-term variability and long-term evolvability of transcriptional responses. Maintaining cellular func- tionality under variable conditions thus enhances gene expression variability and is both a constraint and a driving force for evolution. Department of Genetics, Evolution and Environment, and UCL Cancer Institute, University College London, London WC1E 6BT, UK. Correspondence to J.B. e-mail: jurg@sanger.ac.uk doi:10.1038/nrg2398 Published online 1 July 2008 Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation Luis López-Maury, Samuel Marguerat and Jürg Bähler Abstract | Organisms are constantly exposed to a wide range of environmental changes, including both short-term changes during their lifetime and longer-term changes across generations. Stress-related gene expression programmes, characterized by distinct transcriptional mechanisms and high levels of noise in their expression patterns, need to be balanced with growth-related gene expression programmes. A range of recent studies give fascinating insight into cellular strategies for keeping gene expression in tune with physiological needs dictated by the environment, promoting adaptation to both short- and long-term environmental changes. Not only do organisms show great resilience to external challenges, but emerging data suggest that they also exploit these challenges to fuel phenotypic variation and evolutionary innovation. NATURE REVIEWS | GENETICS VOLUME 9 | AUGUST 2008 | 583 REVIEWS © 2008 Macmillan Publishers Limited. All rights reserved.