Molecular functions of the histone acetyltransferase chaperone complex Rtt109-Vps75

被引:94
作者
Berndsen, Christopher E. [1 ]
Tsubota, Toshiaki [2 ,3 ]
Lindner, Scott E. [1 ]
Lee, Susan [1 ]
Holton, James M. [4 ]
Kaufman, Paul D. [2 ,3 ]
Keck, James L. [1 ]
Denu, John M. [1 ]
机构
[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biomol Chem, Madison, WI 53706 USA
[2] Univ Massachusetts, Sch Med, Program Gene Funct, Worcester, MA 01605 USA
[3] Univ Massachusetts, Sch Med, Program Express & Mol Med, Worcester, MA 01605 USA
[4] Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nsmb.1459
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 k(cat) of histone acetylation by similar to 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 Rtt109. 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.
引用
收藏
页码:948 / 956
页数:9
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