title: Acetylome study in mouse adipocytes identifies targets of SIRT1 deacetylation in chromatin organization and RNA processing.
abstract: SIRT1 is a key protein deacetylase that regulates cellular metabolism through lysine deacetylation on both histones and non-histone proteins. Lysine acetylation is a wide-spread post-translational modification found on many regulatory proteins and it plays an essential role in cell signaling, transcription and metabolism. In mice, SIRT1 has known protective functions during high-fat diet but the acetylome regulated by SIRT1 in adipocytes is not completely understood. Here we conducted acetylome analyses in murine adipocytes treated with small-molecule modulators that inhibit or activate the deacetylase activity of SIRT1. We identified a total of 302 acetylated peptides from 78 proteins in this study. From the list of potential SIRT1 targets, we selected seven candidates and further verified that six of them can be deacetylated by SIRT1 in-vitro. Among them, half of the SIRT1 targets are involved in regulating chromatin structure and the other half is involved in RNA processing. Our results provide a resource for further SIRT1 target validation in fat cells and suggest a potential role of SIRT1 in the regulation of chromatin structure and RNA processing, which may possibly extend to other cell types as well.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: Sun-Yee
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Sim
authors.affiliation: Department of Pharmacology and Toxicology, UTMB at Galveston, TX 77554, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Laboratory of Metabolic Medicine, Singapore Bioimaging Consortium, A*STAR, 11 Biopolis Way, Singapore 138667, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117596, Singapore; Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore.
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Pharmacology and Toxicology, UTMB at Galveston, TX 77554, USA. Electronic address: kazhang@utmb.edu.
authors.forename: Kangling
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), 30 Medical Drive, Singapore 117609, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117596, Singapore; Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Singapore. Electronic address: xu_feng@sics.a-star.edu.sg.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D041721:3T3-L1 Cells; D000107:Acetylation / Q000187:drug effects; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000502:physiology*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D004791:Enzyme Inhibitors; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Chromatin structure; Mouse adipocyte; Protein deacetylation; RNA processing; SIRT1