Circadian rhythms have been identified not only in the brain but also in peripheral organs. How do the central and peripheral clocks interact? Two recent studies that compare circadian gene expression in brain, liver and heart provide us with new clues about their possible relationship.

Our early thinking on circadian rhythmicity was guided by the idea that a central clock — the suprachiasmatic nucleus (SCN) of the hypothalamus — governed our sleep–wake cycles. The subsequent identification of genes with circadian expression patterns in the SCN began to clarify how this brain region might do its job and, at the same time, led to the discovery of circadian clocks in peripheral tissues. This finding prompted a new fundamental question that has begun to be addressed — how do the different clocks interact to control rhythmicity on a global scale? To answer this question, it might be helpful to know the similarities and differences between the circadian patterns of gene expression in different organs. The two new papers shed light on this issue.

Using microarrays, Panda et al. compared circadian gene expression between the SCN and the liver. They identified several hundred cycling transcripts, the products of which regulate key functions of both organs. Remarkably, they found that the peaks of expression of the different transcripts were distributed throughout the circadian cycle, and that most of the transcripts were specific to the SCN or the liver. Storch et al. made a similar comparison between liver and heart, which led them to identify a wide variety of genes with analogous, out-of-phase patterns of circadian expression. Similar to the findings of Panda and colleagues, Storch et al. found that most of the identified genes showed circadian expression in liver or heart, but not in both. However, tissue-specific gene expression could not account for the differences in this case, as most of the transcripts were present in both organs.

Both studies converge on the idea that many key processes are under circadian control throughout the organism, and give us a glimpse of how the different wheels of the clock might work together. Although many of the transcripts differ from organ to organ, the cycling expression of others, such as some genes of the core circadian oscillator, is conserved across different organs. Do they connect the central pinion and the peripheral wheels? Some of the cycling transcripts are candidates for new clock genes or might be responsive to circulating factors that show circadian rhythmicity. How is their expression controlled? This is just the preamble to the instructions on how to build the whole clock.