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Identification of Histone Lysine Acetoacetylation as a Dynamic Post-Translational Modification Regulated by HBO1

文献类型：期刊论文

作者Gao, Yan3; Sheng, Xinlei2; Tan, Doudou4; Kim, SunJoo2,3; Choi, Soyoung3; Paudel, Sanjita3; Lee, Taeho3; Yan, Cong4; Tan, Minjia4; Kim, Kyu Min1
刊名ADVANCED SCIENCE
出版日期2023-06-29
页码11
关键词acetoacetate acetoacetylation epigenetics HBO1 histone marks novel histone modification
DOI10.1002/advs.202300032
通讯作者Huang, He(hhuang@simm.ac.cn) ; Zhao, Yingming(yingming.zhao@uchicago.edu) ; Lee, Sangkyu(sangkyu@skku.edu)
英文摘要Ketone bodies have long been known as a group of lipid-derived alternative energy sources during glucose shortages. Nevertheless, the molecular mechanisms underlying their non-metabolic functions remain largely elusive. This study identified acetoacetate as the precursor for lysine acetoacetylation (Kacac), a previously uncharacterized and evolutionarily conserved histone post-translational modification. This protein modification is comprehensively validated using chemical and biochemical approaches, including HPLC co-elution and MS/MS analysis using synthetic peptides, Western blot, and isotopic labeling. Histone Kacac can be dynamically regulated by acetoacetate concentration, possibly via acetoacetyl-CoA. Biochemical studies show that HBO1, traditionally known as an acetyltransferase, can also serve as an acetoacetyltransferase. In addition, 33 Kacac sites are identified on mammalian histones, depicting the landscape of histone Kacac marks across species and organs. In summary, this study thus discovers a physiologically relevant and enzymatically regulated histone mark that sheds light on the non-metabolic functions of ketone bodies.
WOS关键词METABOLIC-REGULATION ; GENE-EXPRESSION
资助项目National Research Foundation of Korea (NRF) - Korea government (MSIP)[2021R1A2C1003510] ; National Research Foundation of Korea (NRF) - Korea government (MSIP)[2021K2A9A2A06044011] ; University of Chicago ; Nancy and Leonard Florsheim family fund ; National Institutes of Health (NIH)[GM135504] ; National Institutes of Health (NIH)[AR078555] ; National Institutes of Health (NIH)[CA251677] ; National Natural Science Foundation of China[81973164] ; Shanghai Municipal Science and Technology Major Project[72296]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001018549000001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/306331]  
专题中国科学院上海药物研究所
通讯作者Huang, He; Zhao, Yingming; Lee, Sangkyu
作者单位1.Chosun Univ, Coll Nat Sci, Dept Biomed Sci, Gwangju 61452, South Korea
2.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA
3.Kyungpook Natl Univ, Coll Pharm, Daegu 41566, South Korea
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.Chosun Univ, Coll Pharm, Gwangju 61452, South Korea
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
7.Sungkyunkwan Univ, Sch Pharm, Suwon 16419, South Korea
推荐引用方式
GB/T 7714		 Gao, Yan,Sheng, Xinlei,Tan, Doudou,et al. Identification of Histone Lysine Acetoacetylation as a Dynamic Post-Translational Modification Regulated by HBO1[J]. ADVANCED SCIENCE,2023:11.
APA Gao, Yan.,Sheng, Xinlei.,Tan, Doudou.,Kim, SunJoo.,Choi, Soyoung.,...&Lee, Sangkyu.(2023).Identification of Histone Lysine Acetoacetylation as a Dynamic Post-Translational Modification Regulated by HBO1.ADVANCED SCIENCE,11.
MLA Gao, Yan,et al."Identification of Histone Lysine Acetoacetylation as a Dynamic Post-Translational Modification Regulated by HBO1".ADVANCED SCIENCE (2023):11.

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来源：上海药物研究所

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