Murphy et al show that differentiation of erythroid maturation is accompanied by decreased histone posttranslational modifications associated with active transcription (H3K36me2/3; H3K79me2) but no change in repressive marks (H3K27me2/3; H3K9me2/3), except for H3K20me, which increases during maturation and is known to be associated with chromatin compaction in erythroid cells. In intermediate erythroblasts, there is an increased Poll II–pausing index at nonerythroid genes. In mature erythroblasts, Pol II levels decline, and recruitment is restricted to erythroid genes. Professional illustration by Patrick Lane, ScEYEnce Studios.