The classical view of nuclear receptor action postulates the static binding of liganded receptors to the promoter. We have discovered, however, that nuclear receptors interact dynamically with regulatory elements in living cells, and have proposed the hit-and-run hypothesis for receptor function. Two separate, ATP-dependent mechanisms have been implicated in rapid exchange, the first related to chromatin remodelling, and a second involving molecular chaperone action. We have also observed that steroid receptor responsive promoters move through a complex series of activity states, a phenomenon we term promoter progression. Genome-wide profiling of glucocorticoid receptor (GR) regulated loci reveals several classes of response, including genes that are transiently activated and genes that are transiently repressed. Thus receptor action either leads to a series of events programmed into each promoter, or the receptor and/or associated factors are subject to a time-dependent modification of their activity states. These findings illustrate the complexity of the GR response and indicate the dynamic nature of hormone action throughout the eucaryotic genome.
University of Bristol (2007) Proc Physiol Soc 5, SA5
Research Symposium: Transcription factor mobility and promoter progression
Gordon Hager1, R. L Schiltz1, M. Wiench1, T. Johnson1, T. Voss1, Y. Qiu1, S. John1
1. Laboratory of Receptor Biology & Gene Expression, NCI, NIH, Bethesda, MD, USA.
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