Figure 6

Regulation of splicing factor expression by the circadian clock. (a) Heat-map illustrating the circadian expression profiles of the probesets corresponding to the 62 splicing factors (SFs)/RNA binding proteins (RBPs) from Grosso et al. [40] that were defined as significantly rhythmic in Hughes et al. [41]. For each probeset, the RMA abundances were smoothed with a five point moving average, then rescaled to a z-score relative to the time-course. For each gene, highly similar probesets were removed. Similar circadian expression profiles were clustered on the heat-map using hierarchical clustering. (b) Plots of QPCR and microarray data through time for two exemplar rhythmic SFs, Ddx46 and Rbms1 (see Figure S5 in Additional file 1 for the others). QPCR data: n = 6 and standard error of the mean (SEM). Microarray data: equivalent circadian times in the two days were averaged and expressed relative to CT0 on the first day. Only time points with equivalents in the QPCR dataset were plotted. Error bars represent SEM. Inset: r² and P-value associated with Pearson correlation between QPCR and microarray data. (c) Expression patterns of Ddx46 (left, example of phase-advanced group) and Rbms1 (right, example of arrhythmic group) in the Vipr2^-/- liver. In each case, n = 3 and SEM. GE, gene expression; wt, wild type.