Input-normalized modification levels of H3K4me1 (A), H3K4me2 (B), H3K4me3 (C), and H3K27me3 (D) depend on expression level and promoter type. Transcriptional start sites with a nearby CpG island (CpG+, yellow) show a relatively constant distribution of the H3K4me1 and H3K4me2 modifications levels that does not strongly correlate with gene expression. H3K4me3 levels are correlated with gene expression, even though they exhibit large variability. On the other hand, CpG− promoters (green) are usually unmodified except at high expression levels, where they begin to show higher levels of modifications. Thus, for the most part, the correlation of histone modifications and gene expression is due to a gradual increase in the proportion of CpG+ promoters at higher expression levels. The distribution of H3K27me3 is different, in accordance with its association with repression. At low expression levels, both CpG− and CpG+ promoters are occupied, and the overall levels of H3K27me3 modification decrease with increasing expression.
