DNA microarray analyses of circadian timing: the genomic basis of biological time

Many aspects of physiology and behaviour are organized around a daily rhythm, driven by an endogenous circadian clock. Studies across numerous taxa have identified interlocked autoregulatory molecular feedback loops which underlie circadian organization in single cells. Until recently, little was known of (i) how the core clock mechanism regulates circadian output and (ii) what proportion of the cellular transcriptome is clock regulated. Studies using DNA microarray technology have addressed these questions in a global fashion and identified rhythmically expressed genes in numerous tissues in the rodent (suprachiasmatic nucleus, pineal gland, liver, heart, kidney) and immortalized fibroblasts, in the head and body of Drosophila, in the fungus Neurospora and the higher plant Arabidopsis. These clock controlled genes represent 0.5-9% of probed genes, with functional groups covering a broad spectrum of cellular pathways. There is considerable tissue specificity, with only approximately 10% rhythmic genes common to at least one other tissue, principally consisting of known clock genes. The remaining common genes may constitute genes operating close to the clock mechanism or novel core clock components. Microarray technology has also been applied to understand input pathways to the clock, identifying potential signalling components for clock resetting in fibroblasts, and elucidating the temperature entrainment mechanism in Neurospora. This review explores some of the common themes found between tissues and organisms, and focuses on some of the striking connections between the molecular core oscillator and aspects of circadian physiology and behaviour. It also addresses the limitations of the microarray technology and analyses, and suggests directions for future studies.