Research ArticleTranscriptional Regulation

HES1 Is a Master Regulator of Glucocorticoid Receptor–Dependent Gene Expression

Science Signaling  03 Dec 2013:
Vol. 6, Issue 304, pp. ra103
DOI: 10.1126/scisignal.2004389

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Stress Response Suppressor

Stress induces the adrenal gland to release glucocorticoids, which activate nuclear receptors that initiate changes in gene transcription. HES1 encodes a transcription factor that is activated by Notch signaling during developmental events. Revollo et al. found that glucocorticoids suppressed the expression of HES1 in adult mice and that HES1 protein consequently disappeared from the promoters of glucocorticoid-regulated genes. Mice lacking HES1 in the liver developed glucose intolerance, a metabolic abnormality that was corrected by removal of the adrenal gland. However, administration of exogenous glucocorticoids in adrenalectomized animals restored this glucose intolerance in HES1-deficient mice. These results suggest that HES1 prevents transcriptional activation of glucocorticoid-regulated genes under unstressed conditions and that suppression of HES1 is required for transcriptional responses to glucocorticoids.