Acetylated histone H4 tail enhances histone H3 tail acetylation by altering their mutual dynamics in the nucleosome

The structural unit of eukaryotic chromatin is a nucleosome, compris-ing two histone H2A-H2B heterodimers and one histone (H3-H4)2 tet-ramer, wrapped around by similar to 146 bp of DNA. The N-terminal flexible histone tails stick out from the histone core and have extensive post -translational modifications, causing epigenetic changes of chromatin. Although crystal and cryogenic electron microscopy structures of nu-cleosomes are available, the flexible tail structures remain elusive. Using NMR, we have examined the dynamics of histone H3 tails in nucleosomes containing unmodified and tetra-acetylated H4 tails. In unmodified nucleosome, the H3 tail adopts a dynamic equilib-rium structure between DNA-contact and reduced-contact states. In acetylated H4 nucleosome, however, the H3 tail equilibrium shifts to a mainly DNA-contact state with a minor reduced-contact state. The acetylated H4 tail is dynamically released from its own DNA-contact state to a reduced-contact state, while the H3 tail DNA-contact state becomes major. Notably, H3 K14 in the acety-lated H4 nucleosome is much more accessible to acetyltransferase Gcn5 relative to unmodified nucleosome, possibly due to the for-mation of a favorable H3 tail conformation for Gcn5. In summary, each histone tail adopts a characteristic dynamic state but regu-lates one other, probably creating a histone tail network even on a nucleosome.