Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF

Nucleosome Remodeling Factor (NURF) is an ATP-dependent nucleosome remodeli ng complex that alters chromatin structure by catalyzing nucleosome sliding , thereby exposing DNA sequences previously associated with nucleosomes. We systematically studied how the unstructured N-terminal residues of core hi stories (the N-terminal histone tails) influence nucleosome sliding. We use d bacterially expressed Drosophila histories to reconstitute hybrid nucleos omes lacking one or more histone N-terminal tails. Unexpectedly, we found t hat removal of the N-terminal tail of histone H2B promoted uncatalyzed nucl eosome sliding during native gel electrophoresis. Uncatalyzed nucleosome mo bility was enhanced by additional removal of other histone tails but was no t affected by hyperacetylation of core histories by p300. In addition, we f ound that the N-terminal tail of the histone H4 is specifically required fo r ATP-dependent catalysis of nucleosome sliding by NURF. Alanine scanning m utagenesis demonstrated that H4 residues 16-KRHR-19 are critical for the in duction of nucleosome mobility, revealing a histone tail motif that regulat es NURF activity. An exchange of histone tails between H4 and H3 impaired N URF-induced sliding of the mutant nucleosome, indicating that the location of the KRHR motif in relation to global nucleosome structure is functionall y important. Our results provide functions for the N-terminal histone tails in regulating the mobility of nucleosomes.