SIRT6 exhibits nucleosome-dependent deacetylase activity

Reuven Gil, Shaul Barth, Yariv Kanfi, Haim Y. Cohen

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


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.

Original languageEnglish
Pages (from-to)8537-8545
Number of pages9
JournalNucleic Acids Research
Issue number18
StatePublished - Oct 2013

Bibliographical note

Funding Information:
Israel Science Foundation, I-Core foundation, Israeli Ministry of Health and the ERC: European Research Council. Funding for open access charge: ERC.


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