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Science 298 (5594): 840-843

Copyright © 2002 by the American Association for the Advancement of Science

Oscillatory Expression of the bHLH Factor Hes1 Regulated by a Negative Feedback Loop

Hiromi Hirata,1 Shigeki Yoshiura,1 Toshiyuki Ohtsuka,1* Yasumasa Bessho,1 Takahiro Harada,2 Kenichi Yoshikawa,2 Ryoichiro Kageyama1dagger

Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important for coordinated somite segmentation. However, the molecular mechanism of such oscillation remains to be determined. Here, we show that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity. Cycling is cell-autonomous and depends on negative autoregulation of hes1 transcription and ubiquitin-proteasome-mediated degradation of Hes1 protein. Because Hes1 oscillation can be seen in many cell types, this clock may regulate timing in many biological systems.

1 Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
2 Department of Physics, Graduate School of Science, Kyoto University and CREST, Kyoto 606-8502, Japan.
*   Present address: Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.

dagger    To whom correspondence should be addressed. E-mail: rkageyam{at}virus.kyoto-u.ac.jp

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