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ID:35451821
大小:58.48 KB
页数:4页
时间:2019-03-24
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1、文献阅读+信度与权威分析生命学院D201577459林生彦《LargeconserveddomainsoflowDNAmethylationmaintainedbyDnmt3a》Summary:GainsandlossesinDNAmethylationareprominentfeaturesofmammaliancelltypes.TogaininsightintothemechanismsthatpromoteshiftsinDNAmethylationandcontributetochangesincellfate,includingmalignanttran
2、sformation,weperformedgenome-widemappingof5-methylcytosineand5・hydroxymethylcytosineinpurifiedmousehematopoieticstemcells・Wediscoveredextendedregionsoflowmethylation(canyons)thatspanconserveddomainsfrequentlycontainingtranscriptionfactorsandaredistinctfromCpGislandsandshores・Abouthalfo
3、fthegenesinthesemethylationcanyonsarecoatedwithrepressivehistonemarks,whereastheremainderarecoveredbyactivatinghistonemarksandarehighlyexpressedinhematopoieticstemcells(HSCs).Canyonbordersaredemarkedby5-hydroxyrnethylcytosineandbecomeerodedintheabsenceofDNAmethyltransferase3a(Dnmt3a).G
4、enesdysregulatedinhumanleukemiasareenrichedforcanyon-associatedgenes・Thenewepigeneticlandscapewedescribemayprovideamechanismfortheregulationofhematopoiesisandmaycontributetoleukemiadevelopment.摘要:(屮文)DNA甲基化的积累和丢失是哺乳动物细胞中显著存在的特征。为了深刻解析促进DNA甲基化的发生以及导致细胞命运变化的机制(包括恶性转化),我们在纯净的小鼠造血细胞中进行了5■甲
5、基胞吨唏以及5■疑甲基胞喘噪全基因组比对。我们发现,低甲基化部分的延伸区跨越了转录因子频率较高的保守结构域,而这个区域与CpG岛是截然不同的。在这个甲基化延伸区,将近一半的基因表面含有具有抑制作用的组蛋白标记,而剩余部位则被具有活性的组蛋白标记覆盖,并且在造血细胞(HSCs)中高表达。(低甲基化部分)延伸区边缘被5■瓮甲基胞喘噪分隔开,并且在DNA甲基转移酶3a(Dnmt3a)缺乏的情况下被侵蚀掉。在人类白血病中,基因的调节异常丰富了(低甲基化部分)延伸区边缘的基因。我们描述的这个新表观遗传现象也许能为造血作用的调节作用提供一种机制,并可能对白血病的发展有贡献。《T
6、heR882HDNMT3AMutationAssociatedwithAMLDominantlyInhibitsWild-TypeDNMT3AbyBlockingItsAbilitytoFormActiveTetramers》Summary:SomaticmutationsinDNMT3A,whichencodesadenovoDNAmethyltransferase,arefoundin30%ofnormalkaryotypeacutemyeloidleukemia(AML)cases・MostmutationsareheterozygousandalterR88
7、2withinthecatalyticdomain(mostcommonlyR882H),suggestingthepossibilityofdominant-negativeconsequences・ThemethyltransferaseactivityofR882HDNMT3Aisreducedby80%comparedwiththeWTenzyme.InvitromixingofWTandR882HDNMT3AdoesnotaffecttheWTactivity,butcoexpressionofthetwoproteinsincellsprofound
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