Volume 11 Issue 6
May  2020
Turn off MathJax
Article Contents
Qingfei Zheng, Igor Maksimovic, Akhil Upad, Yael David. Non-enzymatic covalent modifications: a new link between metabolism and epigenetics[J]. Protein&Cell, 2020, 11(6): 401-416. doi: 10.1007/s13238-020-00722-w
Citation: Qingfei Zheng, Igor Maksimovic, Akhil Upad, Yael David. Non-enzymatic covalent modifications: a new link between metabolism and epigenetics[J]. Protein&Cell, 2020, 11(6): 401-416. doi: 10.1007/s13238-020-00722-w

Non-enzymatic covalent modifications: a new link between metabolism and epigenetics

doi: 10.1007/s13238-020-00722-w
  • Received Date: 2020-03-10
  • Rev Recd Date: 2020-04-02
  • Epigenetic modifications, including those on DNA and histones, have been shown to regulate cellular metabolism by controlling expression of enzymes involved in the corresponding metabolic pathways. In turn, metabolic flux influences epigenetic regulation by affecting the biosynthetic balance of enzyme cofactors or donors for certain chromatin modifications. Recently, non-enzymatic covalent modifications (NECMs) by chemically reactive metabolites have been reported to manipulate chromatin architecture and gene transcription through multiple mechanisms. Here, we summarize these recent advances in the identification and characterization of NECMs on nucleic acids, histones, and transcription factors, providing an additional mechanistic link between metabolism and epigenetics.
  • loading
  • [1]
    Allaman I, Bélanger M, Magistretti PJ (2015) Methylglyoxal, the dark side of glycolysis. Front Neurosci 9:23
    Ammar R, Torti D, Tsui K, Gebbia M, Durbic T, Bader GD, Giaever G, Nislow C (2012) Chromatin is an ancient innovation conserved between Archaea and Eukarya. Elife 1:e00078
    Ariga H, Takahashi-Niki K, Kato I, Maita H, Niki T, Iguchi-Ariga SM (2013) Neuroprotective function of DJ-1 in Parkinson's disease. Oxid Med Cell Longev 2013:683920
    Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381-395
    Basu MK, Koonin EV (2005) Evolution of eukaryotic cysteine sulfinic acid reductase, sulfiredoxin (Srx), from bacterial chromosome partitioning protein ParB. Cell Cycle 4:947-952
    Bierhaus A, Fleming T, Stoyanov S, Leffler A, Babes A, Neacsu C, Sauer SK, Eberhardt M, Schnölzer M, Lasitschka F et al (2012) Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy. Nat Med 18:926-933
    Bollong MJ, Lee G, Coukos JS, Yun H, Zambaldo C, Chang JW, Chin EN, Ahmad I, Chatterjee AK, Lairson LL et al (2018) A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling. Nature 562:600-604
    Bondoc FY, Bao Z, Hu WY, Gonzalez FJ, Wang Y, Yang CS, Hong JY (1999) Acetone catabolism by cytochrome P450 2E1:studies with CYP2E1-null mice. Biochem Pharmacol 58:461-463
    Chauvin JR, Pratt DA (2017) On the reactions of thiols, sulfenic acids, and sulfinic acids with hydrogen peroxide. Angew Chem Int Ed Engl 56:6255-6259
    Chen Y, Qin W, Li Z, Guo Z, Liu Y, Lan T, Wang C (2019) Sitespecific chemoproteomic profiling of targets of glyoxal. Future Med Chem 11:2979-2987
    Commerford SL, Carsten AL, Cronkite EP (1982) Histone turnover within nonproliferating cells. Proc Natl Acad Sci USA 79:1163-1165
    Cripps MJ, Hanna K, Lavilla C Jr, Sayers SR, Caton PW, Sims C, De Girolamo L, Sale C, Turner MD (2017) Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. Sci Rep 7:13313
    Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV et al (2019) The microbiota-gut-brain axis. Physiol Rev 99:1877-2013
    Cui Y, Li X, Lin J, Hao Q, Li XD (2017) Histone ketoamide adduction by 4-oxo-2-nonenal is a reversible posttranslational modification regulated by Sirt2. ACS Chem Biol 12:47-51
    Cuthbert GL, Daujat S, Snowden AW, Erdjument-Bromage H, Hagiwara T, Yamada M, Schneider R, Gregory PD, Tempst P, Bannister AJ et al (2004) Histone deimination antagonizes arginine methylation. Cell 118:545-553
    Dalmasso G, Cougnoux A, Delmas J, Darfeuille-Michaud A, Bonnet R (2014) The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microbes 5:675-680
    Distler MG, Palmer AA (2012) Role of Glyoxalase 1 (Glo1) and methylglyoxal (MG) in behavior:recent advances and mechanistic insights. Front Genet 3:250
    Doorn JA, Petersen DR (2002) Covalent modification of amino acid nucleophiles by the lipid peroxidation products 4-hydroxy-2-nonenal and 4-oxo-2-nonenal. Chem Res Toxicol 15:1445-1450
    Drazic A, Myklebust LM, Ree R, Arnesen T (2016) The world of protein acetylation. Biochim Biophys Acta 1864:1372-1401
    Drozak J, Veiga-da-Cunha M, Vertommen D, Stroobant V, Van Schaftingen E (2010) Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J Biol Chem 285:9346-9356
    Duan X, Kelsen SG, Merali S (2008) Proteomic analysis of oxidative stress-responsive proteins in human pneumocytes:insight into the regulation of DJ-1 expression. J Proteome Res 7:4955-4961
    Erler J, Zhang R, Petridis L, Cheng X, Smith JC, Langowski J (2014) The role of histone tails in the nucleosome:a computational study. Biophys J 107:2911-2922
    Etchegaray JP, Mostoslavsky R (2016) Interplay between metabolism and epigenetics:A nuclear adaptation to environmental changes. Mol Cell 62:695-711
    Fournet M, Bonté F, Desmoulière A (2018) Glycation damage:A possible hub for major pathophysiological disorders and aging. Aging Dis 9:880-900
    Gaffney DO, Jennings EQ, Anderson CC, Marentette JO, Shi T, Schou Oxvig AM, Streeter MD, Johannsen M, Spiegel DA, Chapman E et al (2019) Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell Chem Bio. https://doi.org/10.1016/j.chembiol.2019.11.005
    Galligan JJ, Rose KL, Beavers WN, Hill S, Tallman KA, Tansey WP, Marnett LJ (2014) Stable histone adduction by 4-oxo-2-nonenal:a potential link between oxidative stress and epigenetics. J Am Chem Soc 136:11864-11866
    Galligan JJ, Wepy JA, Streeter MD, Kingsley PJ, Mitchener MM, Wauchope OR, Beavers WN, Rose KL, Wang T, Spiegel DA et al(2018) Methylglyoxal-derived posttranslational arginine modifications are abundant histone marks. Proc Natl Acad Sci U S A 115:9228-9233
    García-Giménez JL, Òlaso G, Hake SB, Bönisch C, Wiedemann SM, Markovic J, Dasí F, Gimeno A, Pérez-Quilis C, Palacios O et al (2013) Histone H3 glutathionylation in proliferating mammalian cells destabilizes nucleosomal structure. Antioxid Redox Signal 19:1305-1320
    Geerlings SE, Hoepelman AI (1999) Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol 26:259-265
    Greetham D, Vickerstaff J, Shenton D, Perrone GG, Dawes IW, Grant CM (2010) Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae. BMC Biochem 11:3
    Guo CJ, Chang FY, Wyche TP, Backus KM, Acker TM, Funabashi M, Taketani M, Donia MS, Nayfach S, Pollard KS et al (2017) Discovery of reactive microbiota-derived metabolites that inhibit host proteases. Cell 168:517-526
    Hake SB, Allis CD (2006) Histone H3 variants and their potential role in indexing mammalian genomes:the "H3 barcode hypothesis". Proc Natl Acad Sci USA 103:6428-6435
    Hand CE, Honek JF (2005) Biological chemistry of naturally occurring thiols of microbial and marine origin. J Nat Prod 68:293-308
    Harmel R, Fiedler D (2018) Features and regulation of nonenzymatic post-translational modifications. Nat Chem Biol 14:244-252
    Hellwig M, Henle T (2014) Baking, ageing, diabetes:a short history of the Maillard reaction. Angew Chem Int Ed Engl 53(39):10316-10329
    Jakubowski H (2000) Homocysteine thiolactone:metabolic origin and protein homocysteinylation in humans. J Nutr 130:377S-381S Janke R, Dodson AE, Rine J (2015) Metabolism and epigenetics. Annu Rev Cell Dev Biol 31:473-496
    Jaramillo R, Shuck SC, Chan YS, Liu X, Bates SE, Lim PP, Tamae D, Lacoste S, O'Connor TR, Termini J (2017) DNA Advanced glycation end products (DNA-AGEs) are elevated in urine and tissue in an animal model of type 2 diabetes. Chem Res Toxicol 30:689-698
    Jawahar MC, Murgatroyd C, Harrison EL, Baune BT (2015) Epigenetic alterations following early postnatal stress:a review on novel aetiological mechanisms of common psychiatric disorders. Clin Epigenet 7:122
    Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074-1080
    Jiang T, Zhou X, Taghizadeh K, Dong M, Dedon PC (2007) N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage. Proc Natl Acad Sci USA 104:60-65
    Kansanen E, Kuosmanen SM, Leinonen H, Levonen AL (2013) The Keap1-Nrf2 pathway:Mechanisms of activation and dysregulation in cancer. Redox Biol 1:45-49
    Kawai Y, Garduño L, Theodore M, Yang J, Arinze IJ (2011) Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates its transcriptional activity and nucleocytoplasmic localization. J Biol Chem 286:7629-7640
    Keum YS (2011) Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane:implications of posttranslational modifications. Ann N Y Acad Sci 1229:184-189
    Kim NY, Goddard TN, Sohn S, Spiegel DA, Crawford JM (2019) Biocatalytic reversal of advanced glycation end product modification. Chembiochem 20:2402-2410
    Kopelman P (2007) Health risks associated with overweight and obesity. Obes Rev 1:13-17
    Lee JY, Song J, Kwon K, Jang S, Kim C, Baek K, Kim J, Park C (2012) Human DJ-1 and its homologs are novel glyoxalases. Hum Mol Genet 21:3215-3225
    Li J, Liu D, Sun L, Lu Y, Zhang Z (2012) Advanced glycation end products and neurodegenerative diseases:mechanisms and perspective. J Neurol Sci 317:1-5
    Li Z, Quan G, Jiang X, Yang Y, Ding X, Zhang D, Wang X, Hardwidge PR, Ren W, Zhu G (2018) Effects of metabolites derived from gut microbiota and hosts on pathogens. Front Cell Infect Microbiol 8:314
    Linetsky M, Shipova E, Cheng R, Ortwerth BJ (2007) Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins. Biochim Biophys Acta 1782:22-34
    Little WC, Zile MR, Kitzman DW, Hundley WG, O'Brien TX, Degroof RC (2005) The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 11:191-195
    Maksimovic I, Ray D, Zheng Q, David Y (2019) Utilizing intein transsplicing for in vivo generation of site-specifically modified proteins. Methods Enzymol 626:203-222
    Marinho HS, Real C, Cyrne L, Soares H, Antunes F (2014) Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol 2:535-562
    Matafome P, Sena C, Seiça R (2013) Methylglyoxal, obesity, and diabetes. Endocrine 43:472-484
    Matsuda R, Bi C, Anguizola J, Sobansky M, Rodriguez E, Vargas Badilla J, Zheng X, Hage B, Hage DS (2013) Studies of metabolite-protein interactions:a review. J Chromatogr B Analyt Technol Biomed Life Sci 966:48-58
    Matsuda N, Kimura M, Queliconi BB, Kojima W, Mishima M, Takagi K, Koyano F, Yamano K, Mizushima T, Ito Y et al (2017) Parkinson's disease-related DJ-1 functions in thiol quality control against aldehyde attack in vitro. Sci Rep 7:12816
    May-Zhang LS, Yermalitsky V, Huang J, Pleasent T, Borja MS, Oda MN, Jerome WG, Yancey PG, Linton MF, Davies SS (2018) Modification by isolevuglandins, highly reactive γ-ketoaldehydes, deleteriously alters high-density lipoprotein structure and function. J Biol Chem 293:9176-9187
    McGinty RK, Tan S (2015) Nucleosome structure and function. Chem Rev 115:2255-2273
    Mitchell D 3rd, Ritchey LE, Park H, Babitzke P, Assmann SM, Bevilacqua PC (2018) Glyoxals as in vivo RNA structural probes of guanine base-pairing. RNA 24:114-124
    Moellering RE, Cravatt BF (2013) Functional lysine modification by an intrinsically reactive primary glycolytic metabolite. Science 341:549-553
    Montellier E, Gaucher J (2019) Targeting the interplay between metabolism and epigenetics in cancer. Curr Opin Oncol 31:92-99
    Nair DN, Prasad R, Singhal N, Bhattacharjee M, Sudhakar R, Singh P, Thanumalayan S, Kiran U, Sharma Y, Sijwali PS (2018) A conserved human DJ1-subfamily motif (DJSM) is critical for antioxidative and deglycase activities of Plasmodium falciparum DJ1. Mol Biochem Parasitol 222:70-80
    Näsström T, Fagerqvist T, Barbu M, Karlsson M, Nikolajeff F, Kasrayan A, Ekberg M, Lannfelt L, Ingelsson M, Bergström J (2011) The lipid peroxidation products 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote the formation of α-synuclein oligomers with distinct biochemical, morphological, and functional properties. Free Radic Biol Med 50:428-437
    Obata T (2006) Diabetes and semicarbazide-sensitive amine oxidase (SSAO) activity:a review. Life Sci 79:417-422
    Ochs R (2019) An idea to explore:understanding redox reactions in biochemistry. Biochem Mol Biol Educ 47:25-28
    Parrish JP, Kastrinsky DB, Wolkenberg SE, Igarashi Y, Boger DL (2003) NA alkylation properties of yatakemycin. J Am Chem Soc 125:10971-10976
    Poole LB (2015) The basics of thiols and cysteines in redox biology and chemistry. Free Radic Biol Med 80:148-157
    Raiber EA, Portella G, Martínez Cuesta S, Hardisty R, Murat P, Li Z, Iurlaro M, Dean W, Spindel J, Beraldi D et al (2018) 5-Formylcytosine organizes nucleosomes and forms Schiff base interactions with histones in mouse embryonic stem cells. Nat Chem 10:1258-1266
    Reid MA, Dai Z, Locasale JW (2017) The impact of cellular metabolism on chromatin dynamics and epigenetics. Nat Cell Biol 19:1298-1306
    Repici M, Giorgini F (2019) DJ-1 in Parkinson's disease:Clinical insights and therapeutic perspectives. J Clin Med 8:1377
    Richarme G, Dairou J (2017) Parkinsonism-associated protein DJ-1 is a bona fide deglycase. Biochem Biophys Res Commun 483:387-391
    Richarme G, Mihoub M, Dairou J, Bui LC, Leger T, Lamouri A (2015) Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal-and glyoxal-glycated cysteine, arginine, and lysine residues. J Biol Chem 290:1885-1897
    Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV, Nadal M, Bouloc P et al (2017) Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science 357:208-211
    Rinschen MM, Ivanisevic J, Giera M, Siuzdak G (2019) Identification of bioactive metabolites using activity metabolomics. Nat Rev Mol Cell Biol 20:353-367
    Rydberg B, Lindahl T (1982) Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. EMBO J 1:211-216
    Sanghvi VR, Leibold J, Mina M, Mohan P, Berishaj M, Li Z, Miele MM, Lailler N, Zhao C, de Stanchina E et al (2019) The oncogenic action of NRF2 depends on de-glycation by fructosamine-3-kinase. Cell 178:807-819
    Schalkwijk CG, Stehouwer CDA (2020) Methylglyoxal, a highly reactive dicarbonyl compound, in diabetes, its vascular complications, and other age-related diseases. Physiol Rev 100:407-461
    Schumacker PT (2006) Reactive oxygen species in cancer cells:live by the sword, die by the sword. Cancer Cell 10:175-176
    Shuck SC, Wuenschell GE, Termini JS (2018) Product studies and mechanistic analysis of the reaction of methylglyoxal with deoxyguanosine. Chem Res Toxicol 31:105-115
    Shuker DE, Prevost V, Friesen MD, Lin D, Ohshima H, Bartsch H (1993) Urinary markers for measuring exposure to endogenous and exogenous alkylating agents and precursors. Environ Health Perspect 99:33-37
    Singh R, Barden A, Mori T, Beilin L (2001) Advanced glycation endproducts:a review. Diabetologia 44:129-146
    Spiro RG (2002) Protein glycosylation:nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds.
    Glycobiology 12:43R-56R Sun R, Fu L, Liu K, Tian C, Yang Y, Tallman KA, Porter NA, Liebler DC, Yang J (2017) Chemoproteomics reveals chemical diversity and dynamics of 4-oxo-2-nonenal modifications in cells. Mol Cell Proteomics 16:1789-1800
    Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M et al (2002) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34:395-402
    Synold T, Xi B, Wuenschell GE, Tamae D, Figarola JL, Rahbar S, Termini J (2008) Advanced glycation end products of DNA:quantification of N2-(1-Carboxyethyl)-2'-deoxyguanosine in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry. Chem Res Toxicol 21:2148-2155
    Szende B, Tyihák E (2010) Effect of formaldehyde on cell proliferation and death. Cell Biol Int 34:1273-1282
    Szwergold BS, Howell S, Beisswenger PJ (2001) Human fructosamine-3-kinase:purification, sequencing, substrate specificity, and evidence of activity in vivo. Diabetes 50:2139-2147
    Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H (2004) DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep 5:213-218
    Talasz H, Wasserer S, Puschendorf B (2002) Nonenzymatic glycation of histones in vitro and in vivo. J Cell Biochem 85:24-34
    Tamae D, Lim P, Wuenschell GE, Termini J (2011) Mutagenesis and repair induced by the DNA advanced glycation end product N2-1-(carboxyethyl)-2'-deoxyguanosine in human cells. Biochemistry 50:2321-2329
    Teodorowicz M, Hendriks WH, Wichers HJ, Savelkoul HFJ (2018) Immunomodulation by Processed Animal Feed:the role of maillard reaction products and advanced glycation end-products(AGEs). Front Immunol 9:2088
    Toyoda Y, Erkut C, Pan-Montojo F, Boland S, Stewart MP, Müller DJ, Wurst W, Hyman AA, Kurzchalia TV (2014) Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival. Biol Open 3:777-784
    Trerotola M, Relli V, Simeone P, Alberti S (2015) Epigenetic inheritance and the missing heritability. Hum Genomics 9:17
    Tzika E, Dreker T, Imhof A (2018) Epigenetics and metabolism in health and disease. Front Genet 9:361
    Van Laer K, Hamilton CJ, Messens J (2013) Low-molecular-weight thiols in thiol-disulfide exchange. Antioxid Redox Signal 18:1642-1653
    Van Schaftingen E, Delpierre G, Collard F, Fortpied J, Gemayel R, Wiame E, Veiga-da-Cunha M (2007) Fructosamine 3-kinase and other enzymes involved in protein deglycation. Adv Enzyme Regul 47:261-269
    Veiga da-Cunha M, Jacquemin P, Delpierre G, Godfraind C, Théate I, Vertommen D, Clotman F, Lemaigre F, Devuyst O, Van Schaftingen E (2006) Increased protein glycation in fructosamine 3-kinase-deficient mice. Biochem J 399:257-264
    Wagner GR, Hirschey MD (2014) Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases. Mol Cell 54:5-16
    Wang Y, Wysocka J, Sayegh J, Lee YH, Perlin JR, Leonelli L, Sonbuchner LS, McDonald CH, Cook RG, Dou Y et al (2004) Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306:279-283
    Wanner MJ, Zuidinga E, Tromp DS, Vilím J, Jørgensen SI, van Maarseveen JH (2020) Synthetic evidence of the Amadori-type alkylation of biogenic amines by the neurotoxic metabolite dopegal. J Org Chem 85:1202-1207
    Wei B, Berning K, Quan C, Zhang YT (2017) Glycation of antibodies:Modification, methods and potential effects on biological functions. MAbs 9:586-594
    Weng X, Gong J, Chen Y, Wu T, Wang F, Yang S, Yuan Y, Luo G, Chen K, Hu L et al (2020) Keth-seq for transcriptiome wide RNA structure mapping. Nat Chem Biol. https://doi.org/10.1038/s41589-019-0459-3
    Wilson MR, Jiang Y, Villalta PW, Stornetta A, Boudreau PD, Carrá A, Brennan CA, Chun E, Ngo L, Samson LD et al (2019) The human gut bacterial genotoxin colibactin alkylates DNA. Science 363:eaar7785
    Wuenschell GE, Tamae D, Cercillieux A, Yamanaka R, Yu C, Termini J (2010) Mutagenic potential of DNA glycation:miscoding by (R)-and (S)-N2-(1-carboxyethyl)-2'-deoxyguanosine. Biochemistry 49:1814-1821
    Xu Y, Chen X (2006) Glyoxalase II, a detoxifying enzyme of glycolysis byproduct methylglyoxal and a target of p63 and p73, is a pro-survival factor of the p53 family. J Biol Chem 281:26702-26713
    Xu H, Huang W, He QL, Zhao ZX, Zhang F, Wang R, Kang J, Tang GL (2012) Self-resistance to an antitumor antibiotic:a DNA glycosylase triggers the base-excision repair system in yatakemycin biosynthesis. Angew Chem Int Ed Engl 51:10532-10536
    Xu L, Chen J, Gao J, Yu H, Yang P (2015) Crosstalk of homocysteinylation, methylation and acetylation on histone H3. Analyst 140:3057-3063
    Zhang Z, Smith BA, Wang L, Brock A, Cho C, Schultz PG (2003) A new strategy for the site-specific modification of proteins in vivo. Biochemistry 42:6735-6746
    Zhang DD, Lo SC, Cross JV, Templeton DJ, Hannink M (2004) Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex. Mol Cell Biol 24:10941-10953
    Zhang Q, Bai B, Mei X, Wan C, Cao H, Li Dan, Wang S, Zhang M, Wang Z, Wu J et al (2018) Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects. Nat Commun 9:3436
    Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M et al (2019) Metabolic regulation of gene expression by histone lactylation. Nature 574:575-580
    Zheng Q, Prescott NA, Maksimovic I, David Y (2019a) (De)Toxifying the epigenetic code. Chem Res Toxicol 32:796-807
    Zheng Q, Omans ND, Leicher R, Osunsade A, Agustinus AS, FinkinGroner E, D'Ambrosio H, Liu B, Chandarlapaty S, Liu S et al(2019b) Reversible histone glycation is associated with diseaserelated changes in chromatin architecture. Nat Commun 10:1289
    Zheng Q, Osunsade A, David Y (2019) Protein arginine deiminase 4 antagonizes methylglyoxal-induced histone glycation. bioRxiv doi: 10.1101/826818
    Zheng Q, Maksimovic I, Upad A, Guber D, David Y (2020) Synthesis of an alkynyl methylglyoxal probe to investigate nonenzymatic histone glycation. J Org Chem 85:1691-1697
    Zhu Y, Snooks H, Sang S (2018) Complexity of advanced glycation end products in foods:Where are we now? J Agric Food Chem 66:1325-1329
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索


    Article Metrics

    Article views (704) PDF downloads(73) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint