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

• DOI: 10.1021/jacs.1c13555
• Publication Date: 2022-02-17T18:22:40Z
• Authors: Zhipeng A. Wang; Samuel D. Whedon; Mingxuan Wu; Siyu Wang; Edward A. Brown; Ananya Anmangandla; Liam Regan; Kwangwoon Lee; Jianfeng Du; Jun Young Hong; Louise Fairall; Taylor Kay; Hening Lin; Yingming Zhao; John W. R. Schwabe; Philip A. Cole
• Keywords: Sortase; Histone H2B

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 β-hydroxybutyrylated H2Bs were incorporated into nucleosomes investigated as substrates of deacetylase (HDAC) complexes sirtuins. A wide range rates site-specificities observed these enzyme forms suggesting distinct biological roles in regulating chromatin structure epigenetics.