Rabbit Anti-Human GREB1 Polyclonal Antibody

Resveratrol and kaempferol are natural chemopreventative agents that are also aryl hydrocarbon receptor (AHR) antagonists and estrogen receptor (ER) agonists. In this study we evaluated the role of ER alpha in resveratrol- and kaempferol-mediated inhibition of AHR-dependent transcription. Kaempferol or resveratrol inhibited dioxin-induced cytochrome P450 1A1 (CYP1A1) and CYP1B1 expression levels and recruitment of AHR, ER alpha and co-activators to CYP1A1 and CYP1B1. Both phytochemicals induced the expression and recruitment of ER alpha to gene amplified in breast cancer 1 (GREB1). RNAi-mediated knockdown of ER alpha in T-47D cells did not affect the inhibitory action of either phytochemical on AHR activity. Both compounds also inhibited AHR-dependent transcription in ER alpha-negative MDA-MB-231 and BT-549 breast cancer cells. These data show that ER alpha does not contribute to the AHR-inhibitory activities of resveratrol and kaempferol. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Cellular decision-making and environmental adaptation are dependent upon a heterogeneous response of gene expression to external cues. Heterogeneity arises in transcription from random switching between transcriptionally active and inactive states, resulting in bursts of RNA synthesis. Furthermore, the cellular state influences the competency of transcription, thereby globally affecting gene expression in a cell-specific manner. We determined how external stimuli interplay with cellular state to modulate the kinetics of bursting. To this end, single-cell dynamics of nascent transcripts were monitored at the endogenous estrogen-responsive GREB1 locus. Stochastic modeling of gene expression implicated a two-state promoter model in which the estrogen stimulus modulates the frequency of transcriptional bursting. The cellular state affects transcriptional dynamics by altering initiation and elongation kinetics and acts globally, as GREB1 alleles in the same cell correlate in their transcriptional output. Our results suggest that cellular state strongly affects the first step of the central dogma of gene expression, to promote heterogeneity in the transcriptional output of isogenic cells.