24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex
Figure 5
The timing of methylation for DNA methylation sites with high amplitude oscillations is time locked to the timing of peak RNA abundance.
(A) Heat map depicting the time of the nadir of methylation relative to the timing of RNA abundance for the associated transcript, for high amplitude DNA methylation sites (i.e. amplitude of oscillation at least 10% of the mean methylation level) in or near GENCODE v14 annotated transcripts. Negative numbers mean that the nadir of methylation precedes peak RNA abundance and positive numbers indicate that the nadir of methylation follows peak RNA abundance. Red indicates a greater than expected density, while blue indicates a lesser than expected density. (B) The same data depicted as histograms in 1-hour bins. The dark line indicates the timing of peak RNA abundance. The red line indicates the angular mean time of the methylation nadir. The p-value is for Rayleigh's test for uniformity on the circle. The nadirs of methylation for sites in the 2 kb upstream of the transcription start site, the 5′UTR, the 1st exon, and to a lesser extent the 1st intron were significantly temporally clustered relative to the timing of peak RNA abundance (p = 8.1×10−21, p = 1.4×10−15, p = 1.2×10−15, and p = 3.1×10−7 respectively by Rayleigh's test) with the nadir of methylation preceding peak RNA abundance by 1–3 hours. There was no such temporal clustering in other exons, other introns, and the 3′UTR.