Extended Data Fig. 7: Chromatin state analysis of age-related CpGs.

The heatmap color-codes the hypergeometric overlap analysis between age-related CpGs (columns) and two groupings of CpGs (1) universal chromatin states analysis¹ and (2) binding by polycomb repressive complex 1 and 2 (PRC1, PRC2) defined based on ChIP-Seq datasets in ENCODE⁵³, see the last two rows. The first column shows a bar plot that reports the proportion of CpGs that are known to be bounded by PRC2 that ranges from zero to one (PRC2). Note that chromatin states that contain a high proportion of PRC2 bound CpGs overlap significantly with the top 1,000 CpGs that increased with age across tissues and mammal species. For each row (chromatin state or PRC annotation), the table reports odds ratios (OR) from hypergeometric test results for the top 1,000 CpGs that increased/decreased with age from meta-EWAS of age across all, blood, skin, liver, muscle, brain and cerebral cortex tissues, respectively. Unadjusted hypergeometric P values based on one-sided are listed in Supplementary Data 8.3–8.9. The heatmap color gradient is based on −log10 (unadjusted hypergeometric P value) multiplied by the sign of OR greater than one. Red colors denote OR greater than one in contrast with blue colors for OR less than one. Legend lists states based on their group category and PRC group. The y-axis lists state or PRC name and number of mammalian array CpGs inside parentheses. The left/right panel lists the results based on the top 1,000 CpGs with positive/negative age correlation. We displayed 63 universal chromatin states that show significant enrichment/depletion at P < 0.001 in any of the tissues. HET, heterochromatin; exon, transcription and exons; weak promoters, bivalent promoters; promoters, promoter flanking.