The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model

doi:10.1074/mcp.M117.067553

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	The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model
	Nie, Litong 1,2,3; Shuai, Lin 2,3; Zhu, Mingrui 2,3; Liu, Ping 1,2; Xie, Zhi-Fu 2,3; Jiang, Shangwen 1,2; Jiang, Hao-Wen 4; Li, Jia2 ; Zhao, Yingming1,2,5 ; Li, Jing-Ya2
刊名	MOLECULAR & CELLULAR PROTEOMICS
	2017-07
卷号	16 期号:7 页码:1324-1334
ISSN号	1535-9476
DOI	10.1074/mcp.M117.067553
文献子类	Article
英文摘要	Type 2 diabetes (T2D) is a major chronic healthcare concern worldwide. Emerging evidence suggests that a histone- modification-mediated epigenetic mechanism underlies T2D. Nevertheless, the dynamics of histone marks in T2D have not yet been carefully analyzed. Using a mass spectrometry-based label-free and chemical stable isotope labeling quantitative proteomic approach, we systematically profiled liver histone post-translational modifications (PTMs) in a prediabetic high-fat diet-induced obese (DIO) mouse model. We identified 170 histone marks, 30 of which were previously unknown. Interestingly, about 30% of the histone marks identified in DIO mouse liver belonged to a set of recently reported lysine acylation modifications, including propionylation, butyrylation, malonylation, and succinylation, suggesting possible roles of these newly identified histone acylations in diabetes and obesity. These histone marks were detected without prior affinity enrichment with an antibody, demonstrating that the histone acylation marks are present at reasonably high stoichiometry. Fifteen histone marks differed in abundance in DIO mouse liver compared with liver from chow-fed mice in label-free quantification, and six histone marks in stable isotope labeling quantification. Analysis of hepatic histone modifications from metformintreated DIO mice revealed that metformin, a drug widely used for T2D, could reverse DIO-stimulated histone H3K36me2 in prediabetes, suggesting that this mark is likely associated with T2D development. Our study thus offers a comprehensive landscape of histone marks in a prediabetic mouse model, provides a resource for studying epigenetic functions of histone modifications in obesity and T2D, and suggest a new epigenetic mechanism for the physiological function of metformin.
资助项目	National Basic Research Program of China (973 Program)[2014CBA02004] ; Natural Science Foundation of China[31370814] ; Natural Science Foundation of China[81470166] ; Natural Science Foundation of China[81302820] ; Strategic Priority Research Program of the Chinese Academy of Sciences, "Personalized Medicines-Molecular Signature-based Drug Discovery and Development"[XDA12020314] ; Shanghai Municipal Science and Technology Commission[14DZ2261100] ; Shanghai Municipal Science and Technology Commission[15410723100] ; National Institute of Health (NIH) of the United States[GM105933] ; National Institute of Health (NIH) of the United States[CA160036] ; National Basic Research Program of China[2016YFC1305500]
WOS关键词	HEPATIC GLUCONEOGENESIS ; LYSINE PROPIONYLATION ; MASS-SPECTROMETRY ; GENE ACTIVATION ; METHYLATION ; METFORMIN ; PROTEIN ; PHOSPHORYLATION ; IDENTIFICATION ; SUCCINYLATION
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
WOS记录号	WOS:000404597500012
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272592]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室化学蛋白质组学研究中心
通讯作者	Li, Jing-Ya; Tan, Minjia
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 4.East China Normal Univ, Coll Chem & Mol Engn, Shanghai 200062, Peoples R China; 5.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA
推荐引用方式 GB/T 7714	Nie, Litong,Shuai, Lin,Zhu, Mingrui,et al. The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model[J]. MOLECULAR & CELLULAR PROTEOMICS,2017,16(7):1324-1334.
APA	Nie, Litong.,Shuai, Lin.,Zhu, Mingrui.,Liu, Ping.,Xie, Zhi-Fu.,...&Tan, Minjia.(2017).The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model.MOLECULAR & CELLULAR PROTEOMICS,16(7),1324-1334.
MLA	Nie, Litong,et al."The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model".MOLECULAR & CELLULAR PROTEOMICS 16.7(2017):1324-1334.