SIRT6 Exhibits Nucleosome-Dependent Deacetylase Activity

Nucleic Acids Res. 2013 Oct;41(18):8537-45. doi: 10.1093/nar/gkt642. Epub 2013 Jul 26.


The SIRT6 deacetylase is a key regulator of mammalian genome stability, metabolism and lifespan. Previous studies indicated that SIRT6 exhibits poor deacetylase activity in vitro. Here, we explored the specific conditions that allow SIRT6 to function as a significant deacetylase. We show that SIRT6 associates with the nucleosome and deacetylates histones H3 and H4 when they are packaged as nucleosomes, but not as free histones. In contrast, SIRT1 shows the opposite characteristics. Thus, our results show that SIRT6 activity is nucleosome dependent, and suggest that its binding to the nucleosome might convert it into an active structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HEK293 Cells
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Nucleosomes / enzymology*
  • Sirtuins / metabolism*


  • Histones
  • Nucleosomes
  • SIRT6 protein, human
  • Sirtuins