蛋氨酸对动物表型性状的影响及DNA甲基化调控机制的研究进展
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摘要
蛋氨酸(methionine,Met)是动物生长代谢过程中重要的甲基供体,同时作为必需氨基酸中唯一的含硫氨基酸,与赖氨酸一起为玉米—豆粕型日粮或微生物蛋白合成的第一或第二限制性氨基酸。另外,Met作为饲料添加剂对动物机体的生产性能、自身免疫力及疾病预防具有重要作用。随着营养表观遗传学在动物领域研究的不断发展,可实现以Met作为重要的营养素对动物进行表观遗传修饰(DNA甲基化、组蛋白修饰、染色质重塑及非编码RNA等)。DNA甲基化作为表观遗传修饰的方式之一,对于研究表型性状具有重要作用,是联系基因和表型间的纽带。文章介绍了DNA甲基化的作用机制及蛋氨酸代谢的调控机制,为今后正确理解Met与表观遗传学修饰之间的联系,进一步揭示表型性状的分子作用机制提供参考。通过基因组学进一步对Met如何在分子水平影响动物表型性状的改变进行展望与分析,也有助于掌握Met需要的个体差异,确定个体的营养需要量,实现真正的"基因饲养"模式。
Methionine(Met) is an important methyl donor in the growth and metabolic process of animal.At the same time,as the only sulfur-containing amino acid in the essential amino acid,it is the first or second restrictive amino acid with lysine to synthesize corn—soybean meal feed or microbial protein.In addition,Met serving as a feed additive plays an important role in animal production performance,autoimmunity and disease prevention.With the development of epigenetics in the field of animal studies,as an important nutrient,Met can be used to carry out epigenetic modifications(DNA methylation,histone modification,chromatin remodelling and non-coding RNA,etc.).DNA methylation is one of the ways of epigenetics,and it has an important role in the study of phenotypic traits,making it a connection between genes and phenotypes.This paper introduces the mechanism of DNA methylation and the regulation of methionine metabolism,which will provide references for understanding the relationship between the Met and epigenetic modification and further revealing the molecular mechanism of phenotypic traits.In addition,through genomics,further prospect and analysis of how Met affects the changes of animal phenotypic traits at the molecular level can also help grasp the individual differences in animal Met demands,determine the individual nutritional requirements,and realize the real "gene breeding" model.
Methionine(Met) is an important methyl donor in the growth and metabolic process of animal.At the same time,as the only sulfur-containing amino acid in the essential amino acid,it is the first or second restrictive amino acid with lysine to synthesize corn—soybean meal feed or microbial protein.In addition,Met serving as a feed additive plays an important role in animal production performance,autoimmunity and disease prevention.With the development of epigenetics in the field of animal studies,as an important nutrient,Met can be used to carry out epigenetic modifications(DNA methylation,histone modification,chromatin remodelling and non-coding RNA,etc.).DNA methylation is one of the ways of epigenetics,and it has an important role in the study of phenotypic traits,making it a connection between genes and phenotypes.This paper introduces the mechanism of DNA methylation and the regulation of methionine metabolism,which will provide references for understanding the relationship between the Met and epigenetic modification and further revealing the molecular mechanism of phenotypic traits.In addition,through genomics,further prospect and analysis of how Met affects the changes of animal phenotypic traits at the molecular level can also help grasp the individual differences in animal Met demands,determine the individual nutritional requirements,and realize the real "gene breeding" model.
引文
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[2] XU S,HARRISON J H,CHALUPA W,et al.The effect of ruminal bypass lysine and methionine on milk yield and composition of lactating cows[J].Journal of Dairy Science,1998,81(4):1062-1077.
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[7] 郑秦文,陈思恋,林欣,等.蛋氨酸羟基类似物异丙酯(HMBi)对福建黄兔屠宰性能、肠道黏膜形态和肠道酶活的影响[J].中国畜牧兽医,2015,42(7):1711-1716. ZHENG Q W,CHEN S L,LIN X,et al.Effect of HMBi on slaughter performance,intestinal mucosal morphology and intestinal enzyme activity of Fujian Yellow rabbits[J].China Animal Husbandry & Veterinary Medicine,2015,42(7):1711-1716.(in Chinese)
[8] 王杰,崔凯,王世琴,等.饲粮蛋氨酸水平对湖羊公羔营养物质消化、胃肠道pH及血清指标的影响[J].动物营养学报,2017,29(8):3004-3013. WANG J,CUI K,WANG S Q,et al.Effects of dietary level of methionine on nutrient digestion,gastrointestinal pH and serum indexes of male Hu lambs[J].Chinese Journal of Animal Nutrition,2017,29(8):3004-3013.(in Chinese)
[9] 王杰,崔凯,王世琴,等.蛋氨酸水平对羔羊体况发育、消化道组织形态及血清抗氧化指标的影响[J].动物营养学报,2017,29(5):1792-1802. WANG J,CUI K,WANG S Q,et al.Effects of methionine level on development of body condition,morphology of digestive tract and serum antioxidant indexes in lambs[J].Chinese Journal of Animal Nutrition,2017,29(5):1792-1802.(in Chinese)
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[11] 宋敏艳,俞英.畜禽表观遗传学主要研究领域及研究进展[J].中国畜牧兽医,2016,43(10):2701-2709. SONG M Y,YU Y.The main research fields and progress of livestock epigenetics[J].China Animal Husbandry & Veterinary Medicine,2016,43(10):2701-2709.(in Chinese)
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[13] SCHNEIDER E,PLIUSHCH G,El H N,et al.Spatial,temporal and interindividual epigenetic variation of functionally important DNA methylation patterns[J].Nucleic Acids Research,2010,38(12):3880-3890.
[14] BIRD A.DNA methylation patterns and epigenetic memory[J].Genes & Development,2002,16(1):6-21.
[15] GOLL M G,BESTOR T H.Eukaryotic cytosine methyltrans-ferases[J].Annual Review of Biochemistry,2005,74:481-514.
[16] FENG Y Q,DESPRAT R,FU H Q,et al.DNA methylation supports intrinsic epigenetic memory in mammalian cells[J].PLoS Genetics,2006,2(4):e65.
[17] LONG H K,BLACKLEDGE N P,KLOSE R J.ZF-CxxC domain-containing proteins,CpG islands and the chromatin connection[J].Biochemical Society transactions,2013,41(3):727-740.
[18] JONES P A,LIANG G N.Rethinking how DNA methylation patterns are maintained[J].Nature Reviews Genetics,2009,10(11):805-811.
[19] MCKAY J A,MATHERS J C.Diet induced epigenetic changes and their in plications for health[J].Acta Physiologica,2011,202(2):103-118.
[20] NELISSEN E C,VAN MONTFOOT A P,DUMOULIN J C,et al.Epigenetics and the placenta[J].Human Reproduction Update,2011,17(3):397-417.
[21] FARIAS N,HO N,BUTLER S,et al.The effects of folic acid on global DNA methylation and colonosphere formation in colon cancer cell lines[J].Journal of Nutrition Biochemistry,2015,26(8):818-826.
[22] JADAVJI N M,BAHOUS R H,DENG L Y,et al.Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism[J].Biochemical Journal,2014,461(2):205-212.
[23] ADAIKALAKOTESWARI A,FINER S,VOYIAS P D,et al.Vitamin B12 insufficiency induces cholesterol biosynthesis by limiting s-adenosylmethionine and modulating the methylation of SREBF1 and LDLR genes[J].Clinical Epigentics,2015,7(2):14.
[24] GOKUL G,KHOSLA S.DNA methylation and Cancer[J].Sub-cellular Biochemistry,2013,21(35):597-625.
[25] LEE H S,KIM B H,CHO N Y,et al.Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma[J].Cancer Research,2009,15(3):812-820.
[26] KAMIYAMA H,SUZUKI K,MAEDA T,et al.DNA demethylation in normal colon tissue predicts predisposition to multiple cancers[J].Oncogene,2012,31(48):5029-5037.
[27] SHAO C,SUN W,TAN M,et al.Integrated,genome-wide screening for hypomethylated oncogenes in salivary gland adenoid cystic carcinoma[J].Cancer Research,2011,17(13):4320-4330.
[28] OOI S K T,BESTOR T H.The colorful history of active DNA demethylation[J].Cell,2008,133(7):1145-1148.
[29] FAVERI L E D,HURST C D,PLATT F M,et al.Putative tumour suppressor gene necdin is hypermethylated and mutated in human cancer[J].British Journal of Cancer,2013,108(6):1368-1377.
[30] WU X Y,CHENG J N,LU L.Vitamin B12 and methionine deficiencies induce genome damage measured using the cytokinesis-block micronucleus cytome assay in human B lymphoblastoid cell lines[J].Nutrition and Cancer-An International Journal,2013,65(6):866-873.
[31] SAENGKERDSUB S,LINGBECK J M,WILKINSON H H,et al.Characterization of isolated yeast growth response to methionine analogs[J].Journal of Environmental Science & Health Part B Pesticides Food Contaminants & Agricultural Wastes,2013,48(12):1112-1120.
[32] MATO J,ALVAREZ L,ORTIZ P,et al.S-adenosylmethionine synthesis:Molecular mechanisms and clinical implications[J].Pharmacology & Therapeutics,1997,73(3):265-280.
[33] LU S C,MATO J M.S-adenosylmethionine in liver health,injury,and cancer[J].Physiological Reviews,2012,92(4):1515-1542.
[34] GROVE T L,BENNER J S,RADLE M I,et al.A radically different mechanism for S-adenosylmethionine-dependent methyltransferases[J].Science,2011,332(6029):604-607.
[35] CHEN N C,YANG F,CAPECCI L M,et al.Regulation of homocysteine metabolism and methylation in human and mouse tissues[J].Experimental Biology,2010,24(8):2804-2817.
[36] BROSNAN J T,BROSNAN M E,BERTOLO F P,et al.Methionine:A metabolically unique amino acid[J].Livestock Science,2007,112(1):72-77.
[37] AGRAWAL V,ALPINI S E,STONE E M,et al.Targeting methionine auxotrophy in cancer:Discovery & exploration[J].Expert Opinion on Biological Therapy,2012,12(1):53-61.
[38] MUDD S H,POOLE J R.Labile methyl balances for normal humans on various dietary regimens[J].Metabolism-clinical & Experimental,1975,24(6):721-735.
[39] TREMOLIZZO L,DOUEIRI M S,DONG E,et al.Valproate corrects the schizophrenia-like epigenetic behavioral modifications induced by methionine in mice[J].Biological Psychiatry,2005,57(5):500-509.
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