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Involvement of CLOCK:BMAL1 heterodimer in serum-responsive mPer1 induction
Hosung Jung1, Youngshik Choe, Hyunjung Kim
1Development and Neuroendocrine Research Laboratory, School of Biomedical Sciences, Seoul National University, Korea.
Neuroreport
|January 25, 2003
Summary
The CLOCK:BMAL1 heterodimer regulates rapid mPer1 gene induction for circadian clock resetting. This protein complex is crucial for phase resetting, impacting clock gene regulation.
Area of Science:
- Chronobiology
- Molecular Biology
- Gene Regulation
Background:
- The rapid induction of mouse period1 (mPer1) gene expression is vital for circadian clock phase resetting.
- The molecular mechanisms underlying this rapid induction remain poorly understood.
- Previous findings suggest the process does not involve new protein synthesis.
Purpose of the Study:
- To investigate the role of the CLOCK:BMAL1 heterodimer in the rapid induction of mPer1 gene expression.
- To test the hypothesis that CLOCK:BMAL1 is involved in mPer1 transcription during phase resetting.
Main Methods:
- Utilized a dominant-negative mutant (CLOCKdelta19) to inhibit CLOCK:BMAL1 function in vitro.
- Assessed serum-evoked mPer1 mRNA expression and promoter activity.
- Measured the DNA binding activity of CLOCK:BMAL1 to the mPer1 promoter E-boxes.
Main Results:
- Interference with CLOCK:BMAL1 function significantly blunted serum-induced mPer1 mRNA expression and promoter activity.
- Serum shock markedly increased CLOCK:BMAL1 heterodimer DNA binding activity to the mPer1 promoter.
- These findings indicate CLOCK:BMAL1's direct involvement in mPer1 transcriptional regulation.
Conclusions:
- The CLOCK:BMAL1 heterodimer plays a critical role in the rapid induction of mPer1 gene expression.
- This mechanism is essential for the phase resetting of the circadian clock.
- CLOCK:BMAL1 functions not only in the core negative feedback loop but also in rapid transcriptional responses.