期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 33, 期 14, 页码 2650-2658出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00094-13
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资金
- NIH [DK064678, NS054941]
- March of Dimes
- Christopher Reeve Foundation
- Research Institute of Pharmaceutical Sciences
- Research Settlement Fund for the new faculty of SNU
- POSCO TJ Park Science Fellowship
- Basic Science Research Program through the National Research Foundation of Korea
- Ministry of Education, Science, and Technology [2012R1A1A1001749, R31-10105]
- National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea [1220120]
- World Class University program through the National Research Foundation of Korea
- Korea Health Promotion Institute [1220120] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012R1A1A1001749] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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