Histone H2B Deacylation Selectivity: Exploring Chromatin's Dark Matter with an Engineered Sortase

被引:34
|
作者
Wang, Zhipeng A. [1 ,2 ]
Whedon, Samuel D. [1 ,2 ]
Wu, Mingxuan [1 ,2 ]
Wang, Siyu [3 ]
Brown, Edward A. [3 ]
Anmangandla, Ananya [4 ]
Regan, Liam [3 ]
Lee, Kwangwoon [1 ,2 ]
Du, Jianfeng [5 ]
Hong, Jun Young [4 ]
Fairall, Louise [3 ]
Kay, Taylor [1 ,2 ]
Lin, Hening [4 ]
Zhao, Yingming [5 ]
Schwabe, John W. R. [3 ]
Cole, Philip A. [1 ,2 ]
机构
[1] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA
[2] Harvard Med Sch, Dept Biol Chem & Mol Pharmcol, Boston, MA 02115 USA
[3] Univ Leicester, Leicester Inst Struct & Chem Biol, Dept Mol & Cell Biol, Leicester LE1 7RH, Leics, England
[4] Cornell Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Ithaca, NY 14853 USA
[5] Ben May Dept Canc Res, Chicago, IL 60637 USA
基金
英国惠康基金;
关键词
METABOLIC-REGULATION; CHEMICAL-SYNTHESIS; GENE-EXPRESSION; DEACETYLASE; DEMETHYLATION; ACETYLATION; RECOGNITION; INHIBITORS; PROTEINS; BIOLOGY;
D O I
10.1021/jacs.1c13555
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We describe a new method to produce histone H2B by semisynthesis with an engineered sortase transpeptidase. N-Terminal tail site-specifically modified acetylated, lactylated, and beta-hydroxybutyrylated histone H2Bs were incorporated into nucleosomes and investigated as substrates of histone deacetylase (HDAC) complexes and sirtuins. A wide range of rates and site-specificities were observed by these enzyme forms suggesting distinct biological roles in regulating chromatin structure and epigenetics.
引用
收藏
页码:3360 / 3364
页数:5
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