title: SIRT7 Is Activated by DNA and Deacetylates Histone H3 in the Chromatin Context.
abstract: Mammalian sirtuins (SIRT1-7) are members of a highly conserved family of nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases that regulate many biological processes including metabolism, genome stability, and transcription. Among the seven human sirtuins, SIRT7 is the least understood, to a large extent due to the lack of enzymatic activity in vitro. Here, we reported that SIRT7 can be activated by DNA to hydrolyze the acetyl group from lysine residues in vitro on histone peptides and histones in the chromatin context. Both N- and C- termini of SIRT7 are important for the DNA-activated deacetylase activity. The regulatory mechanism of SIRT7 is different from that of SIRT6, which also showed increased activity on chromatin substrates, but the deacetylase activity of SIRT6 on a peptide substrate cannot be activated by DNA. This finding provides an improved enzymatic activity assay of SIRT7 that will promote the development of SIRT7 modulators. Further investigation into the activation mechanism of SIRT7 by DNA could provide new insights into its biological function and help the development of sirtuin activators.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tong
authors.affiliation: School of Biomedical Sciences, University of Hong Kong , 21 Sassoon Road, Hong Kong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: David D
authors.initials: DD
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Sushabhan
authors.initials: S
authors.lastname: Sadhukhan
authors.affiliation: School of Biomedical Sciences, University of Hong Kong , 21 Sassoon Road, Hong Kong, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853, United States.|Howard Hughes Medical Institute, Cornell University , Ithaca, New York 14853, United States.
authors.forename: Hening
authors.initials: H
authors.lastname: Lin
mesh_terms: D000107:Acetylation; D002843:Chromatin / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; C510661:SIRT7 protein, human; D037761:Sirtuins