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急性白血病组蛋白甲基化、乙酰化修饰异常的研究 被引量:9

Study on aberration in histone methylation and acetylation in acute leukemia
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摘要 目的 研究急性白血病患者组蛋白H3K4和H3K9甲基化及H3、H4乙酰化的修饰异常.方法 用Western blot方法检测19例急性白血病患者组蛋白H3K4、H3K9甲基化水平及15例急性白血病患者H3、H4乙酰化水平,同时选取9例非肿瘤患者及4名健康志愿者作为对照.结果 19例急性白血病患者组蛋白H3K4甲基化水平(0.220±0.096)低于对照组(0.447±0.186)(P<0.01);H3K9甲基化水平(0.409±0.106)高于对照组(0.168±0.015)(P<0.01).15例急性白血病患者组蛋白H3乙酰化水平(0.128±0.013)低于对照组(0.386±0.104)(P<0.01);H4乙酰化水平(0.096±0.008)低于对照组(0.341±0.096)(P<0.01).结论 急性白血病细胞的组蛋白甲基化、乙酰化修饰存在异常,表现为组蛋白H3K4甲基化水平减低,H3K9甲基化水平增高,组蛋白乙酰化水平呈明显的减低,这些表达的异常均与染色质结构致密、基因转录抑制有关.组蛋白甲基化、乙酰化调控修饰异常与急性白血病的发病可能有关,有可能作为急性白血病治疗的靶点. Objective To study the aberration in histone H3K4 and H3K9 methylation and H3 and H4 acetylation in human acute leukemia(AL) cells.Methods The histone H3K4 and H3K9 methylation and H3 and H4 acetylation were detected by Western blot in 34 AL patients and 13 controls (9 non leukemia patients, 4 healthy volunteers).Results The level of H3K4 methylation was significantly lower in 19 AL patients than in non leukemia(0.220±0.096 vs 0.447±0.186, P 〈 0.01 ), while the level of H3K9 methylation was significantly higher (0.409±0.106 vs 0.168±0.015, P 〈 0.01 ) ; Both level of histone H3 and H4 acetylation in 15 AL patients were significantly lower (H3: 0.128±0.013 vs 0.386±0.104, H4:0.096±0.008 vs 0.341±0.096, respectively, both P 〈 0.01 ).Conclusion Aberration of histone methylation and deficient histone acetylation in AL may represent the markers for an aberrant pest-translational modification of histones and chromatin structure.It might be a potential epigenetic target for anti-leukemia agent.
出处 《中华血液学杂志》 CAS CSCD 北大核心 2010年第8期523-526,共4页 Chinese Journal of Hematology
基金 卫生部科学研究基金、福建卫生教育联合攻关计划(wkj2008-2-55) 福建医科大学科学研究发展专项基金计划(FZS08018) 漳州市科学研究发展计划基金(Z07014)
关键词 乙酰化 甲基化 组蛋白类 白血病 Methylation Acetylation Histone Leukemia
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参考文献19

  • 1Klose RJ,Kauin EM,Zhang YJ.mjC-domain-containing proteins and histone demethylation.Nat Rev Genet,2006,7:715-727.
  • 2Ogawa M,Sakashita K,Zhao XY,et al.Analysis of histone modification around the CpG island region of the p15 gene in acute myeloblastic leukemia.Leuk Res,2007,31:611-621.
  • 3Tischoff I,Wittekind C,Tannapfel A.Role of epigenetic alterations in cholangiocarcinoma.Hepatobil Pancreat Surg,2006,13:274 -279.
  • 4Kondo Y,Shen L,Issa JP.Critical role of histone methylation intumor suppressor gene silencing in colorectal cancer.Mol Cell Biol,2003,23:206-215.
  • 5Yamane K,Tateish IK,Klose RJ,et al.PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation.Mol Cell,2007,25:801-812.
  • 6Minucci S,Nervi C,Lo Coco F,et al.Histone deacetylases:a common molecular target for differentiation treatment of acute myeloid leukemias.Oncogene,2001,20:3110-3115.
  • 7Yamaguchi Y,Kurokawa M,Imai Y,et al.AML1 is functionally yegulated through p300-mediated acetylation on specific lysine residues.J Biol Chem,2004,279:15630-15638.
  • 8Davis JN,McGhee L,Meyers S,et al.The ETO(MTG8) gene family.Gene,2003,303:1-10.
  • 9Hildebrand D,Tiefenbach J,Heinzel T,et al.Multiple regions of ETO cooperate in transcriptional repression.J Biol Chem,2001,276:9889-9895.
  • 10Durst KL,Lutterbach B,Kummalue T,et al.The inv(16) fusion protein associates with corepressors via a smooth muscle myosin heavy-chain domain.Mol Cell Biol,2003,23:607-619.

同被引文献68

  • 1张妍,高宇,王筱金,朱莎,施蓉,金萍,杨友,田英.p73基因DNA甲基化与儿童急性白血病的关系[J].上海交通大学学报(医学版),2011,31(7):942-947. 被引量:5
  • 2刘藕根,黄清水,陈玉,姜美英,梁斌慧,曾敏帆.IFN-γ,IL-10与梅毒患者血清固定形成关系的探讨[J].中国皮肤性病学杂志,2007,21(7):416-417. 被引量:25
  • 3Aagaard L,Laible G,Selenko P,et al.Functional mammalianhomologues of the Drosophila PEV-modifier Su(var)3-9 encodecentromere-associated proteins which complex with the heterochro-matin component M31.EMBO J,1999;18(7):1923-1938.
  • 4Melcher M,Schmid M,Aagaard L,et al.Structure-functionanalysis of SUV39H1 reveals a dominant role in heterochromatinorganization,chromosome segregation,and mitotic progression.Mol Cell Biol,2000;20(10):3728-3741.
  • 5Gerace EL,Halic M,Moazed D.The methyltransferase activity ofClr4Suv39h triggers RNAi independently of histone H3K9 methy-lation.Mol Cell,2010;39(3):360-372.
  • 6Stewart MD,Li J,Wong J,et al.Relationship between histone H3lysine 9 methylation,transcription repression,and heterochromatinprotein 1 recruitment.Mol Cell Biol,2005;25(7):2525-2538.
  • 7El Gazzar M,Yoza BK,Chen XP,et al.G9a and HP1 couple histo-ne and DNA methylation to TNFαtranscription silencing duringendotoxin tolerance.J Biol Chem,2008;283(47):32198-32208.
  • 8Yang YJ,Han JW,Youn HD,et al.The tumor suppressor,parafibromin,mediate his-tone H3 K9 methylation for cyclin D1repression.Nucleic Acids Res,2010;38(2):382-390.
  • 9Litt MD,Simpson M,Gaszner M.Correlation between histonelysine methylation and developmental changes at the chicken beta-globin locus.Science,2001;293(5539):2453-2455.
  • 10Brinkman AB,Roelofsen T,Pennings SW,et al.Histone modifi-cation patterns associated with the human X chromosome.EMBORep,2006;7(6):628-634.

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