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

Bora Lee, Sun Gyun Kim, Juhee Kim, Kwan Yong Choi, Seunghee Lee, Soo Kyung Lee, Jae W. Lee

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The molecular basis underlying the physiologically well-defined orexigenic function of glucocorticoid(Gc) is unclear. Brainspecific 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.

Original languageEnglish (US)
Pages (from-to)2650-2658
Number of pages9
JournalMolecular and Cellular Biology
Volume33
Issue number14
DOIs
StatePublished - Jul 1 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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