Figure 3. Systemically and oscillator-driven circadian liver genes. Circadian liver transcripts were identified in the transgenic mice presented in Figure 2, using genome-wide Affymetrix microarray hybridization with liver RNAs harvested at 4-hour intervals over 2 days from doxycycline-treated and untreated animals (see ref 84). This technique enables the simultaneous quantification of mRNA levels for virtually all of the 15 000 genes that are active in the liver. In doxycycline-treated mice, core clock and clock-controlled genes (CCGs) as well as systemically controlled genes, are expressed in a circadian manner. In mice not receiving doxycycline in the food, only systemically controlled genes are rhythmically expressed. The heat maps below the livers are phase maps of cyclically accumulating transcripts (red for high expression, green for low expression). S stands for mRNAs whose rhythmic transcription is controlled by systemic cues, and S+O stands for transcripts whose rhythmic transcription can be controlled by either systemic cues or hepatocyte oscillators. Comparison of the S+O heat maps of untreated and doxycycline-treated mice reveals that the circadian expression of most genes requires functional hepatocyte clocks. RNA, ribonucleic acid; mRNA, messenger ribonucleic acid.