Fig. 1.

Computational prediction of clock-controlled elements using HMMs. (A) Chromosomal distributions of predicted conserved clock-controlled elements of conserved non-coding regions mapped on the mouse genome. Chromosomal positions of the 100 most significant hits for E-boxes, D-boxes, and RREs are shown (red). (B) Plots of false discovery rates (FDRs) against match scores of HMM searches in three conditions: (1) searches for conserved elements within conserved non-coding regions (red, “Conserved element”), (2) searches for mouse elements within conserved or non-conserved non-coding regions (blue, “Non-coding region”) and (3) searches in the entire genome relaxing both element conservation and search space (orange, “Whole genome”). FDRs in “Conserved elements” search are plotted against the average match score of human and mouse elements. (C) The distributions of distance from transcriptional starts sites (TSSs) for predicted conserved clock-controlled elements of conserved non-coding regions (1,108 E-boxes, 2,314 D-boxes, and 3,288 RREs). The E-box displays a biased distribution of distance from TSSs, while the D-box and RRE show unbiased, near random distributions (“Random E-box,” “Random D-box,” and “Random RRE,” see also SI Appendix). (D) The average expression of transcripts harboring each element exhibit circadian rhythms in the liver. The average expressions of 36 genes with E-boxes, 29 genes with D-boxes, and 34 genes with RREs exhibited significant circadian oscillations (P = 0.01 for E-box, P = 0.0005 for D-box, and P = 0.001 for RRE). Data were normalized so that the average signal intensity over 12-point time courses is 1.0. Estimated peak times of circadian oscillation were also indicated.