AI Article Synopsis
- The Rev-Erb β gene is essential for regulating circadian rhythms, as well as lipid and glucose metabolism, but its transcriptional regulation mechanisms are not fully understood.
- Luciferase and bioluminescence assays showed that specific regions within the Rev-Erb β gene are important for its oscillation and promoter activity, with essential elements identified for maintaining its circadian phase.
- Findings indicate that the E-boxes and D-box in the first intron influence the circadian oscillation phase of Rev-Erb β, providing new insights into its role in the circadian rhythm system.
Article Abstract
Aim: Rev-Erb β gene plays crucial roles in circadian rhythm, lipid and glucose metabolism, and several diseases. The molecular mechanisms of the transcriptional regulation of Rev-Erb β that generate and determine the phase of the circadian oscillation remain unclear.
Methods: We analyzed the Rev-Erb β promoter by luciferase reporter assays, real-time bioluminescence monitoring assays and electrophoretic mobility shift assays.
Results: Luciferase reporter assays indicated that only the 5' region and exon 1 have obvious promoter activity. Real-time bioluminescence monitoring assays revealed that E1, E2, E3, D boxes are important for maintenance of the amplitude of Rev-Erb β oscillation. Based on EMSA results, REV-ERBβ binds ROREs in the Bmal1 promoter region and inhibits Bmal1 promoter activity.
Conclusion: We provide direct evidence that three E-boxes and one D-box located in the first intron are crucial for the phase of circadian oscillation in Rev-Erb β expression and that the sequences upstream from its transcription start site function as a promoter with no circadian regulation. We also found that the E1 box affects the Rev-Erb β oscillation phase. Our results offer new insight into the role of Rev-Erb β in the circadian rhythm system.
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| http://dx.doi.org/10.5551/jat.14381 | DOI Listing |
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