A pacemaker regulates the circadian rhythms in mammals and so far four clock-gene families have been identified. Now, in October 24 Nature, Sato Honma and colleagues at Hokkaido University Graduate School of Medicine, Sapporo, Japan, show that Dec1 and Dec2 — which encode basic helix–loop–helix (bHLH) transcription factors — are also regulators of the mammalian molecular clock, and form a fifth clock-gene family (Journal of Clinical Investigation, 110:1165-1174, October 15, 2002).

Honma et al. examined the effects of Dec1 and Dec2 and observed that these transcription factors repressed Clock/Bmal1-induced transactivation of the mouse Per1 promoter through direct protein–protein interactions with Bmal1 and/or competition for E-box elements. In addition, they showed that Dec1 and Dec2 are expressed in the suprachiasmic nucleus in a circadian fashion.

"The repressive effect of the Decs on circadian transcription suggests that they are negative clock components," writes J.D. Alvarez at the Hospital...

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