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24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex

Figure 4

Sites in gene regions proximate to the transcription start site have a phase and amplitude distinct from other gene regions.

(A) Heat map of the distribution of methylation nadir times for DNA methylation sties in various gene regions, considering all GENCODE v14 transcripts. (B) The same data expressed as histograms. Sites in the 2 kb upstream of the nearest transcription start site and in the 5′UTR, 1st exon, and 1st intron are most likely to reach their methylation nadir in the early morning, while those in other exons/introns, the 3′UTR, noncoding transcripts, and intergenic regions are most likely to peak in the evening (H1 = 14683.8; p<2.2×10-16 by the Rao Test for equality of polar direction). (C) The proportion of DNA methylation sites with high amplitude (peak to trough difference of>10% of the mean methylation level) in each gene region. The 2 kb upstream of the TSS, the 5′UTR, and the 1st exon are relatively enriched in sites with high amplitude oscillations (χ2 51250.8, p<2.2×10−16).

Figure 4

doi: https://doi.org/10.1371/journal.pgen.1004792.g004