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Originally published as MBC in Press, 10.1091/mbc.E05-05-0396 on November 9, 2005

Vol. 17, Issue 2, 555-565, February 2006

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Molecular Mechanism of Cell-autonomous Circadian Gene Expression of Period2, a Crucial Regulator of the Mammalian Circadian ClockFormula

Makoto Akashi *, Tomoko Ichise *, Takayoshi Mamine {dagger}, and Toru Takumi *

* Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan; {dagger} Life Science Laboratory, Material Laboratories, Sony, Shinagawa, Tokyo 144-0001, Japan

Submitted May 5, 2005; Revised October 17, 2005; Accepted November 2, 2005
Monitoring Editor: J. Silvio Gutkind

Although circadian transcription of Period2 (Per2) is fundamental for the generation of circadian rhythm, the molecular mechanism remains unclear. Here we report that cell-autonomous circadian transcription of Per2 is driven by two transcriptional elements, one for rhythm generation and the other for phase control. The former contains the E-box-like sequence (CACGTT) that is sufficient and indispensable to drive oscillation, and indeed circadian transcription factors site-specifically bind to it. Furthermore, the nature of this atypical E-box is different from that of the classical circadian E-box. The current feedback loop model is based mainly on Period1. Our results provide not only compelling evidence in support of this model but also an explanation for a general basic mechanism to produce various patterns in the phase and amplitude of cell-autonomous circadian gene expression.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E05-05-0396) on November 9, 2005.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Toru Takumi (takumi{at}obi.or.jp).




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