ES hotspots are preferentially occupied by activators. A. Overlap of genes in three groups in ES Ng dataset with up- and down-regulated genes upon Oct4 knockdown in ES cells showing hotspots were enriched for only down-regulated genes. B. Fraction of up- and down-regulated genes upon Dnmt and Set1db knock out in three groups in ES Ng dataset showing hotspot enrichment only in Set1db KO down-regulated genes.