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Publication : Brain-specific homeobox factor as a target selector for glucocorticoid receptor in energy balance.

First Author  Lee B Year  2013
Journal  Mol Cell Biol Volume  33
Issue  14 Pages  2650-8
PubMed ID  23671185 Mgi Jnum  J:204481
Mgi Id  MGI:5532633 Doi  10.1128/MCB.00094-13
Citation  Lee B, et al. (2013) Brain-specific homeobox factor as a target selector for glucocorticoid receptor in energy balance. Mol Cell Biol 33(14):2650-8
abstractText  The molecular basis underlying the physiologically well-defined orexigenic function of glucocorticoid (Gc) is unclear. Brain-specific homeobox factor (Bsx) is a positive regulator of the orexigenic neuropeptide, agouti-related peptide (AgRP), in AgRP neurons of the hypothalamic arcuate nucleus. Here, we show that in response to fasting-elevated Gc levels, Gc receptor (GR) and Bsx synergize to direct activation of AgRP transcription. This synergy is dictated by unique sequence features in a novel Gc response element in AgRP (AgRP-GRE). In contrast to AgRP-GRE, Bsx suppresses transactivation directed by many conventional GREs, functioning as a gene context-dependent modulator of GR actions or a target selector for GR. Consistent with this finding, AgRP-GRE drives fasting-dependent activation of a target gene specifically in GR(+) Bsx(+) AgRP neurons. These results define AgRP as a common orexigenic target gene of GR and Bsx and provide an opportunity to identify their additional common targets, facilitating our understanding of the molecular basis underlying the orexigenic activity of Gc and Bsx.
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