Figure 3.

Relationship between CpG methylation at Alu retrotransposons and proximity to methylated and unmethylated promoters. Alu methylation is plotted as a function of distance from the TSS (A) and to the 3′ splice site of the first exon (B) of methylated (red) and unmethylated (blue) first exons. When near unmethylated first exons, Alu elements are also unmethylated. Alu methylation correlates with first-exon methylation when Alus are within ∼1 kb of the TSS or 3′ edge of the first exon. (C) Negative selection of Alu elements near unmethylated promoters. The ratio of the fraction of methylated promoters with Alus near the first exon to the fraction of unmethylated promoters with Alus near the first exon is plotted as a function of the distance to the TSS. This suggests that unmethylated Alus near promoters are deleterious and are lost from the population by selection. (D) The methylation status of the three major classes of Alu retrotransposons. Note that AluY (the only active Alu in the human genome) remains heavily methylated, even at very high CpG densities.