Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, United States; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
Christopher J Millard
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
Chia-Liang Lin
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
Jennifer E Gurnett
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
Mingxuan Wu
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, United States; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, United States; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
Louise Fairall
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom
Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, United States; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States
Histone acetylation regulates chromatin structure and gene expression and is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit complexes influence deacetylase activities and site-selectivities in chromatin is poorly understood. Previously we reported the results of studies on the HDAC1 containing CoREST complex and acetylated nucleosome substrates which revealed a notable preference for deacetylation of histone H3 acetyl-Lys9 vs. acetyl-Lys14 (Wu et al, 2018). Here we analyze the enzymatic properties of five class I HDAC complexes: CoREST, NuRD, Sin3B, MiDAC and SMRT with site-specific acetylated nucleosome substrates. Our results demonstrate that these HDAC complexes show a wide variety of deacetylase rates in a site-selective manner. A Gly13 in the histone H3 tail is responsible for a sharp reduction in deacetylase activity of the CoREST complex for H3K14ac. These studies provide a framework for connecting enzymatic and biological functions of specific HDAC complexes.
