Understanding stress through the genome.
Stress-induced glucocorticoid hormones support coping with and adaptation to different stressors. They act to modulate gene expression in a tissue and stressor-specific manner through activation of corticosteroid receptors, which act as transcription factors. Here, a number of recent insights in gene regulation under the influence of glucocorticoids are discussed. Emphasis is put on distinct classes of target genes that may be defined, based on categorization of (combinations of) transcription factor binding sites in responsive genes. These categories depend on insights into different mechanisms of transcriptional regulation, such as transactivation vs transrepression, and high affinity vs low affinity hormone receptor response elements. It is argued that such classes, based on mechanistic understanding of transcription regulation, in combination with the availability of complete genomic sequences and expression data from different organs, may enhance our understanding of the way in which organisms deal with different forms of stress.
Meijer
O C
OC
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and Leiden University Medical Center, PO Box 9503, Leiden, 2300 RA, The Netherlands. o.meijer@lacdr.leidenuniv.nl
D000818:Animals; D005786:Gene Expression Regulation; D016678:Genome; D015894:Genome, Human; D006801:Humans; D008954:Models, Biological; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D014158:Transcription, Genetic
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid