journal article Oct 25, 2002

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

View at Publisher Save 10.1126/science.1074560
Abstract
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.
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References
30
[7]
Holley S. A., Geisler R., Nüsslein-Volhard C., Genes Dev. 14, 1678 (2000). 10.1101/gad.14.13.1678
[10]
H. Hirata R. Kageyama data not shown.
[11]
See supporting data on Science Online.
[16]
THE UBIQUITIN SYSTEM

Avram Hershko, Aaron Ciechanover

Annual Review of Biochemistry 10.1146/annurev.biochem.67.1.425
[20]
A synthetic oscillatory network of transcriptional regulators

Michael B. Elowitz, Stanislas Leibler

Nature 10.1038/35002125
[28]
J. K. Dale et al. Nature in press.
[30]
We thank D. Ish-Horowicz and O. Pourquié for critical reading of an earlier version of the manuscript and communicating their results before publication G. Huang for technical help T. Sudo for Hes1 antibody T. Honjo for Delta-expressing cells (D10) and S. Nagatafor pEF-BOS. Supported by research grants from the Ministry of Education Culture Sports Science and Technology of Japan and the Japan Society for the Promotion of Science.
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