Summary
This dissertation identifies the transcription factor Runx2 as a rhythmically expressed gene in the suprachiasmatic nucleus (SCN) that participates in a reciprocal regulatory relationship with the core clock gene Bmal1. While primarily basic science, these findings broaden understanding of the molecular mechanisms governing circadian rhythm amplitude and period, which underpin the biological responses to lighting interventions.
Key Findings
- Runx2 shows rhythmic expression in the SCN, olfactory bulb, and paraventricular nucleus of adult mice, dependent on functional BMAL1 activity.
- BMAL1 directly binds putative E-box sites in the RUNX2 promoter, confirming direct transcriptional regulation.
- Runx2 haplodeficiency and in vitro silencing of RUNX2 resulted in dampened amplitude of rhythmic Bmal1 expression and lengthening of the free-running period of both molecular and behavioral (running wheel) rhythms.
- RUNX2 was found to bind a putative site in the BMAL1 promoter, indicating bidirectional (reciprocal) regulation between Runx2 and the core clock network.
Categories
The Science of Light: Investigates core molecular clock machinery in the SCN, identifying Runx2 as a novel component of the circadian transcriptional-translational feedback loop.
Author(s)
ME Reale
Publication Year
2012
Related Publications
The Science of Light
- Phototransduction by retinal ganglion cells that set the circadian clock
- Color appearance models
- The mammalian circadian timing system: organization and coordination of central and peripheral clocks
- Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice
- Melanopsin is required for non-image-forming photic responses in blind mice