SIRT7 Is Activated by DNA and Deacetylates Histone H3 in the Chromatin Context

ACS Chemical Biology
Zhen TongHening Lin

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.

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Citations

Dec 21, 2016·ACS Chemical Biology·Zhen TongHening Lin
Apr 21, 2017·Nucleic Acids Research·Maximilian F BlankIngrid Grummt
Jan 18, 2017·Medicinal Research Reviews·Matthias SchiedelManfred Jung
Jun 22, 2017·Marine Drugs·Minna K Rahnasto-RillaRuin Moaddel
Jan 11, 2020·Chemistry : a European Journal·Michael BaekChristian A Olsen
May 7, 2020·The Journal of Biological Chemistry·Kelsey S KalousBrian C Smith
Apr 25, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Sören SwyterManfred Jung
Dec 19, 2018·Frontiers in Endocrinology·Jie SongLiang Feng
Aug 23, 2018·Frontiers in Physiology·Rebecca M Parodi-RullánSabzali Javadov
Dec 5, 2018·Frontiers in Endocrinology·Di WuWei-Guo Zhu
Apr 27, 2019·Journal of Biomolecular Structure & Dynamics·Marta HałasaDariusz Matosiuk
Mar 16, 2019·Current Opinion in Chemical Biology·Tatsiana KosciukHening Lin
Dec 7, 2018·Biochemical and Biophysical Research Communications·Ji-Hye KimKwang Rok Kim
Aug 26, 2021·Biological Chemistry·Anna-Theresa BlaslMichael Lammers
Oct 17, 2020·ACS Medicinal Chemistry Letters·Nima RajabiChristian A Olsen
Jan 18, 2019·Journal of the American Chemical Society·Wesley Wei WangWenshe Ray Liu

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