title: Sirtuins 1 and 2 Are Universal Histone Deacetylases.
abstract: Lysine acetylation serves as an epigenetic marker for myriad cellular processes, such as signaling, differentiation, DNA repair, angiogenesis, and the like. Sirtuin 1 (SIRT1) and sirtuin 2 (SIRT2) are NAD(+)-dependent histone deacetylases that operate as post-translational regulators for the deacetylation of acetyllysine. Here, we discuss the ability for SIRT1 and SIRT2 to deacetylate monoacetylated histone H3 on two separate architectures-the peptide and the nucleosome. In addition, we analyze the site-specificity of SIRT1 and SIRT2 on 10 different monoacetylated histone H3 nucleosomes. By utilizing a rapid screening array, SIRT1 and SIRT2 were found to demonstrate heightened enzymatic activity when incubated with nucleosomal substrates over their peptide counterparts. These two enzymes displayed little site-specificity among the acetyl-nucleosomes screened, contrary to previous expectations, as well. The implication of the overall nonspecificity of SIRT1 and SIRT2 on the nucleosome suggests that these sirtuin enzymes have an adaptive nature, harnessing an ability to respond to various cellular situations, rather than an enzyme specifically designed for a particular task or function.
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Willie W
authors.initials: WW
authors.lastname: Hsu
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Wenshe R
authors.initials: WR
authors.lastname: Liu
mesh_terms: D002460:Cell Line; D003001:Cloning, Molecular; D004926:Escherichia coli; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009154:Mutation; D009707:Nucleosomes; D017510:Protein Folding; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009707:Nucleosomes; C447939:SIRT1 protein, human; C474199:SIRT2 protein, human; D056564:Sirtuin 1; D056565:Sirtuin 2