Together, we highlight how, 50 years on, the nucleosome still has surprising and unexplored roles in orchestrating the functional genome. Who knows what's left to be uncovered.

Moreover, evolution has used this repeatedly, as H2A.Zs from across eukaryotic diversity have acquired a physical interaction with the transcription elongation factor Spt6, driving its recruitment to chromatin and increasing transcription processivity.

We show that histones are more than just barriers to transcription--they can also directly interact with the transcription apparatus through their core domain, shaping its activity.