Histone H2B Deacylation Selectivity: Exploring Chromatin’s Dark Matter with an Engineered Sortase
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
Abstract
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 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.
Topics & Concepts
ChemistryNucleosomeHistoneAcetylationSortaseChromatinHistone deacetylaseChromatin remodelingHistone H2BEpigeneticsBiochemistryCell biologyDNAGeneBacterial proteinBiologyBiochemical and Structural CharacterizationUbiquitin and proteasome pathwaysMachine Learning in Bioinformatics