Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF.
Nucleosome Remodeling Factor (NURF) is an ATP-dependent nucleosome remodeling 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 histones (the N-terminal histone tails) influence nucleosome sliding. We used bacterially expressed Drosophila histones to reconstitute hybrid nucleosomes lacking one or more histone N-terminal tails. Unexpectedly, we found that removal of the N-terminal tail of histone H2B promoted uncatalyzed nucleosome sliding during native gel electrophoresis. Uncatalyzed nucleosome mobility was enhanced by additional removal of other histone tails but was not affected by hyperacetylation of core histones by p300. In addition, we found that the N-terminal tail of the histone H4 is specifically required for ATP-dependent catalysis of nucleosome sliding by NURF. Alanine scanning mutagenesis demonstrated that H4 residues 16-KRHR-19 are critical for the induction of nucleosome mobility, revealing a histone tail motif that regulates NURF activity. An exchange of histone tails between H4 and H3 impaired NURF-induced sliding of the mutant nucleosome, indicating that the location of the KRHR motif in relation to global nucleosome structure is functionally important. Our results provide functions for the N-terminal histone tails in regulating the mobility of nucleosomes.
Hamiche
A
A
Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Kang
J G
JG
Dennis
C
C
Xiao
H
H
Wu
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009068:Movement; D016296:Mutagenesis; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D006657:Histones; D019476:Insect Proteins; D009707:Nucleosomes; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate