Acetylation of vertebrate H2A.Z and its effect on the structure of the nucleosome.
Purified histone H2A.Z from chicken erythrocytes and a sodium butyrate-treated chicken erythroleukemic cell line was used as a model system to identify the acetylation sites (K4, K7, K11, K13, and K15) and quantify their distribution in this vertebrate histone variant. To understand the role played by acetylation in the modulation of the H2A.Z nucleosome core particle (NCP) stability and conformation, an extensive analysis was conducted on NCPs reconstituted from acetylated forms of histones, including H2A.Z and recombinant H2A.Z (K/Q) acetylation mimic mutants. Although the overall global acetylation of core histones destabilizes the NCP, we found that H2A.Z stabilizes the NCP regardless of its state of acetylation. Interestingly and quite unexpectedly, we found that the change in NCP conformation induced by global histone acetylation is dependent on H2A/H2A.Z acetylation. This suggests that acetylated H2A variants act synergistically with the acetylated forms of the core histone complement to alter the particle conformation. Furthermore, the simultaneous occurrence of H2A.Z and H2A in heteromorphic NCPs that most likely occurs in vivo slightly destabilizes the NCP, but only in the presence of acetylation.
Ishibashi
Toyotaka
T
Department of Biochemistry and Microbiology and The Center for Biomedical Research, University of Victoria, Petch Building, Victoria, BC, Canada V8W 3P6.
Dryhurst
Deanna
D
Rose
Kristie L
KL
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
Ausió
Juan
J
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002645:Chickens; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004357:Drug Synergism; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism*
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; C077020:histone H2A.F-Z