Program in Gene Function and Expression
Amino Acid Sequence; Animals; Catalytic Domain; Crystallography, X-Ray; Enzyme Activation; Histone Acetyltransferases; Histones; Kinetics; Models, Molecular; Molecular Chaperones; Molecular Sequence Data; Multiprotein Complexes; Protein Structure, Tertiary; Recombinant Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Static Electricity; Substrate Specificity; Xenopus Proteins; Xenopus laevis
Genetics and Genomics
Histone acetylation and nucleosome remodeling regulate DNA damage repair, replication and transcription. Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones. In vitro analysis of Rtt109 revealed that Vps75, a Nap1 family histone chaperone, could also stimulate Rtt109-dependent acetylation of H3K56. However, the molecular function of the Rtt109-Vps75 complex remains elusive. Here we have probed the molecular functions of Vps75 and the Rtt109-Vps75 complex through biochemical, structural and genetic means. We find that Vps75 stimulates the kcat of histone acetylation by approximately 100-fold relative to Rtt109 alone and enhances acetylation of K9 in the H3 histone tail. Consistent with the in vitro evidence, cells lacking Vps75 showed a substantial reduction (60%) in H3K9 acetylation during S phase. X-ray structural, biochemical and genetic analyses of Vps75 indicate a unique, structurally dynamic Nap1-like fold that suggests a potential mechanism of Vps75-dependent activation of Rttl09. Together, these data provide evidence for a multifunctional HAT-chaperone complex that acetylates histone H3 and deposits H3-H4 onto DNA, linking histone modification and nucleosome assembly.
DOI of Published Version
Nat Struct Mol Biol. 2008 Sep;15(9):948-56. Link to article on publisher's website
Nature structural and molecular biology
Berndsen CE, Tsubota T, Lindner SE, Lee S, Holton JM, Kaufman PD, Keck JG, Denu JM. (2008). Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75. Program in Gene Function and Expression Publications. https://doi.org/10.1038/nsmb.1459. Retrieved from https://escholarship.umassmed.edu/pgfe_pp/88