Temporal relationships of Pol II, H3K4me3, H3K36me3 profiles, and mRNA accumulation in mouse liver.

<p>(A) Phase histograms for cyclic genes. A selection of 284 genes (<i>p</i><0.004, FDR = 0.3) showing cyclic patterns in all marks (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001442#s4" target="_blank">Materials and Methods</a>) were fitted with a cosine function and the phase (peak time of the fit) was computed. These phases show a bimodal distribution for Pol II occupancy in promoters and gene bodies with maxima around ZT9 and ZT21, as well as in mRNA accumulation with a phase delay of approximately 3 h. (B) Phases for the same genes are represented in pairs, with color shade indicating <i>p</i> value (lower <i>p</i> values are darker) for the 24-h rhythm of the Pol II promoter signal. Relative to the phase of Pol II in promoters, we find high concordance for Pol II occupancy phases in gene bodies, an average delay of 1.3 h for H3K4me3 phases, and more spread H3K36me3 and mRNA phases with an average delay of about 3 h. Colored lines are mean-square regressions with intercepts corresponding to the average delays, as indicated in color. The thin dashed lines indicate ±2 h delays. (C) Temporal cross-correlation analysis. Using the same gene selection, we applied Fourier interpolation to obtain a continuous time trace (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001442#pbio-1001442-g003" target="_blank">Figure 3C,D</a> and <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001442#pbio-1001442-g004" target="_blank">Figure 4D,E</a>) and computed average cross-correlations between each mark and the corresponding Pol II promoter trace. Pol II occupancies in promoters and gene bodies are well-correlated and simultaneous, and H3K4me3 lags by about 1 h on average, whereas mRNA and H3K36me3 are phase-delayed by about 3 h. The same figure is shown for a more permissive selection (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001442#pbio.1001442.s008" target="_blank">Figure S8</a>, <i>n</i> = 752, <i>p</i><0.018, FDR = 0.5).