SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis

  1. Alejandro Vaquero2,6,
  2. Michael B. Scher2,6,
  3. Dong Hoon Lee2,
  4. Ann Sutton3,
  5. Hwei-Ling Cheng4,
  6. Frederick W. Alt1,4,
  7. Lourdes Serrano5,
  8. Rolf Sternglanz3, and
  9. Danny Reinberg1,2,7
  1. 1 Howard Hughes Medical Institute,
  2. 2 Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA;
  3. 3 Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5215, USA;
  4. 4 The Children’s Hospital and The CBR Institute for Biomedical Research, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;
  5. 5 Department of Genetics, Human Genetics Institute, Rutgers University, Piscataway, New Jersey 08854, USA
  1. 6

    ↵6 These authors contributed equally to this work.

Abstract

The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD+-dependent protein deacetylases involved in caloric restriction-dependent life span extension. We found that SirT2 and its yeast counterpart Hst2 have a strong preference for histone H4K16Ac in their deacetylation activity in vitro and in vivo. We have pinpointed the decrease in global levels of H4K16Ac during the mammalian cell cycle to the G2/M transition that coincides with SirT2 localization on chromatin. Mouse embryonic fibroblasts (MEFs) deficient for SirT2 show higher levels of H4K16Ac in mitosis, in contrast to the normal levels exhibited by SirT1-deficient MEFs. The enzymatic conversion of H4K16Ac to its deacetylated form may be pivotal to the formation of condensed chromatin. Thus, SirT2 is a major contributor to this enzymatic conversion at the time in the cell’s life cycle when condensed chromatin must be generated anew.

Keywords

Footnotes

| Table of Contents

This Article

  1. Published in Advance April 28, 2006, doi: 10.1101/gad.1412706 Genes & Dev. 20: 1256-1261 Copyright © 2006, Cold Spring Harbor Laboratory Press

Article Category

Share

Current Issue

  1. February 1, 2024, 38 (3-4)
  1. Current Issue
  1. Alert me to new issues of G&D

Life Science Alliance