简介:Itisstandardpractice,wheneveraresearcherfindsanewgene,tosearchdatabasesforgenesthathaveasimilarsequence.Itisnotstandardpractice,wheneveraresearcherfindsanewgene,tosearchforgenesthathavesimilarexpression(coexpression).Failuretoperformco-expressionsearcheshasleadtoincorrectconclusionsaboutthelikelyfunctionofnewgenes,andhasleadtowastedlaboratoryattemptstoconfirmfunctionsincorrectlypredicted.WepresentheretheexampleofGliaMaturationFactorgamma(GMF-gamma).Despiteitsname,ithasnotbeenshowntoparticipateingliamaturation.ItisageneofunknownfunctionthatissimilarinsequencetoGMF-beta.ThesequencehomologyandchromosomallocationledtoanunsuccessfulsearchforGMF-gammamutationsinglioma.WeexaminedGMF-gammaexpressionin1432humancDNAlibraries.Highestexpressionoccursinphagocytic,antigen-presentingandotherhematopoieticcells.WefoundGMF-gammamRNAinalmosteverytissueexamined,withexpressioninnervoustissuenohigherthaninanyothertissue.OurevidenceindicatesthatGMF-gammaparticipatesinphagocytosisinantigenpresentingcells.Searchesforgeneswithsimilarsequencesshouldbesupplementedwithsearchesforgeneswithsimilarexpressiontoavoidincorrectpredictions.
简介:导致的模仿的微严肃(SMG)的知识在微生物的致病力变化为长期的空间飞行的成功是重要的。在用高方面比率容器生物反应器的以前的研究,当在建模的微严肃成长时,我们证明酵母种类Saccharomycescerevisiae经历了重要phenotypic回答,它在基因表达侧面的分析被反映。在这研究,我们证实Candidaalbicans以一种类似的方式对SMG作出回应,证明在到这个环境压力的酵母之中有保存回答。我们也报导C的生长。在SMG的albicans导致与提高的致病力一致的一个morphogenic开关。明确地,我们在有机体的细丝状的形式观察了增加,在二基因的表示伴随变化与酵母菌丝的转变联系了。词法反应可以为宇航员的安全有重要含意,当真菌的病原体可以在空间飞行期间变得更剧毒。
简介:Inthepost-genomicera,identificationofspecificregulatorymotifsortranscrip-tionfactorbindingsites(TFBSs)innon-codingDNAsequences,whichisessentialtoelucidatetranscriptionalregulatorynetworks,hasemergedasanobstaclethatfrustratesmanyresearchers.Consequently,numerousmotifdiscoverytoolsandcorrelateddatabaseshavebeenappliedtosolvingthisproblem.However,theseexistingmethods,basedondifferentcomputationalalgorithms,showdiversemotifpredictionefficiencyinnon-codingDNAsequences.Therefore,understandingthesimilaritiesanddifferencesofcomputationalalgorithmsandenrichingthemotifdiscoveryliteraturesareimportantforuserstochoosethemostappropriateoneamongtheonlineavailabletools.Moreover,therestilllackscrediblecriteriontoassessmotifdiscoverytoolsandinstructionsforresearcherstochoosethebestaccordingtotheirownprojects.Thusintegrationoftherelatedresourcesmightbeagoodapproachtoimproveaccuracyoftheapplication.Recentstudiesintegrateregulatorymotifdiscoverytoolswithexperimentalmethodstoofferacomplemen-taryapproachforresearchers,andalsoprovideamuch-neededmodelforcurrentresearchesontranscriptionalregulatorynetworks.HerewepresentacomparativeanalysisofregulatorymotifdiscoverytoolsforTFBSs.
简介:Transcriptionfactor(TF)bindingtoitsDNAtargetsiteplaysanessentialroleingeneregulation.Thelocation,orientationandspacingoftranscriptionfactorbindingsites(TFBSs)alsoaffectregulatoryfunctionoftheTF.However,hownucleosomalcontextofTFBSsinfluencesTFbindingandsubsequentgeneregulationremainstobeelucidated.Usinggenome-widenucleosomepositioningandTFbindingdatainbuddingyeast,wefoundthatbindingaffinitiesofTFstoDNAtendtodecreasewithincreasingnucleosomeoccupancyoftheassociatedbindingsites.WefurtherdemonstratedthatnucleosomalcontextofbindingsitesiscorrelatedwithgeneregulationofthecorrespondingTF.Nucleosome-depletedTFBSsarelinkedtohighgeneactivityandlowexpressionnoise,whereasnucleosome-coveredTFBSsareassociatedwithlowgeneactivityandhighexpressionnoise.Moreover,nucleosome-coveredTFBSstendtodisruptcoexpressionofthecorrespondingTFtargetgenes.WeconcludethatnucleosomalcontextofbindingsitesinfluencesTFbindingaffinity,subsequentlyaffectingtheregulationofTFsontheirtargetgenes.ThisemphasizestheneedtoincludenucleosomalcontextofTFBSsinmodelinggeneregulation.
简介:理解控制全球基因表达模式的改变的规章的机制继续是在计算生物学的一项挑战性的任务。我们以前开发了一个蚂蚁算法,为微数组数据的一种生物学上启发的计算技术,和预言的通常认为的抄写因素绑定主题(TFBM)通过模仿国王自然蚂蚁的交互行为。这里,我们把算法扩大了到一套基于万维网的软件,蚂蚁Modeler,并且使用了它调查transcriptional机制内在的骨头形成。机械装载和骨头morphogenic蛋白质(BMP)的管理是二个已知的处理加强骨头。我们探讨了一个问题:有任何TFBM,刺激“机械装载的anabolism的回答”并且“调停BMP的osteogenic发信号”吗?尽管在在二回答的基因之中没有重要重叠,比较基于模型的分析建议二个独立osteogenic过程采用普通TFBM,例如一个压力为peroxisome的应答的元素和一个主题激活proliferator的受体(PPAR)。在用老鼠造骨细胞房间的vitro分析的modeling以后响应机械装载支持了象PPAR,Ikaros3,和LMO2那样的预言的TFBM的参与。总起来说,结果将是有用的导出一套可试验的假设并且在骨头形成的复杂transcriptional控制检验特定的管理者的角色。
简介:Werecentlyreportedtheuseofagene-trappingapproachtoisolatecellclonesinwhichareportergenehadintegratedintogenesmodulatedbyT-cellactivation.WehavenowtestedapanelofclonesfromthatreportandidentifiedtheonethatrespondstoavarietyofG-proteincoupledreceptors(GPCR).TheβlactamasetaggedEGR-3JurkatcellwasusedtodissectspecificGPCRsignalinginvivo.ThreeGPCRswerestudied,includingthechemokinereceptorCXCR4(Gicoupled)thatwasendogenouslyexpressed,theplateletactivationfactor(PAF)receptor(Gq-coupled),andβ2adrenergicreceptor(Gs-coupled)thatwasbothstablytransfected.Agonistsforeachreceptoractivatedtranscriptionoftheβ-lactamasetaggedEGR-3gene.InductionofEGR-3throughCXCR4wasblockedbypertussistoxinandPD58059,aspecificinhibitorofMEK(MAPK/ERKkinase).NeitheroftheseinhibitorsblockedisoproterenolorPAF-mediatedactivationofEGR-3.Conversely,β2-andPAF-mediatedEGR-3activationwasblockedbythep38,specificinhibitorSB580.Inaddition,bothβ2-andPAF-mediatedEGR-3activationcouldbesynergisticallyactivatedbyCXCR4activation.ThiscombinedresultindicatesthatEGR-3canbeactivatedthroughdistinctsignaltransductionpathwaysbydifferentGPCRsandthatsignalscanbeintegratedandamplifiedtoefficientlytunethelevelofactivation.
简介:Shigellaflexneriisaninfectiouspathogenthatcausesdysenterytohuman,whichremainsaseriousthreattopublichealth,particularlyindevelopingcountries.Inthisstudy,theglobalproteinexpressionpatternsofS.flexneriduringtransitionfromexponentialgrowthtostationaryphaseinvitrowereanalyzedbyusing2-DPAGEcombinedwithMALDI-TOFMS.Inatime-courseexperimentwithfivetimepoints,therelativeabundanceof49proteinspotsvariedsignificantly.In-terestingly,aputativeoutermembraneproteinYciD(OmpW)wasalmostnotdetectedintheexponentialgrowthphasebutbecameoneofthemostabundantproteinsinthewholestationary-phaseproteome.SomeproteinsregulatedbytheglobalregulatorFNRwerealsosignificantlyinduced(suchasAnsB,AspA,FrdAB,andKatG)orrepressed(suchasAceEF,OmpX,SodA,andSucAB)duringthegrowthphasetransition.Theseproteinsmaybethekeyeffectorsofthebacterialcellcycleorplayimportantrolesinthecellularmaintenanceandstressresponses.Ourexpressionprofiledataprovidevaluableinformationforthestudyofbacterialphysiologyandformthebasisforfutureproteomicanalysesofthispathogen.
简介:人的造血作用用控制干细胞区别的技术被评估,二维的胶化基于电气泳动的proteomics,和功能的基因组学。我们提供神经胶质成熟因素鲸鱼群妈(GMFG)是cytokine应答的蛋白质在的第一份报告导致erythropoietin并且刺激导致因素的造血的系开发的granulocyte殖民地。从全球功能的基因组学分析的结果显示GMFG拥有几个另外的特征:造血的织物特定的基因表示,与高分数的造血作用特定的抄写因素集中的一个倡导者,和有一个原始血/免疫者系统的可能的分子的coevolution。根据我们的调查结果,我们假设那GMFG是可以调停的造血特定的蛋白质人的造血的干细胞的pluripotentiality和系承诺。
简介:Thecommonapproachtofindco-regulatedgenesistoclustergenesbasedongeneexpression.However,duetothelimitedinformationpresentinanydataset,genesinthesameclustermightbeco-expressedbutnotnecessarilyco-regulated.Inthispaper,weproposetointegrateknowntranscriptionfactorbindingsiteinformationandgeneexpressiondataintoasingleclusteringscheme.Thisschemewillfindclustersofco-regulatedgenesthatarenotonlyexpressedsimilarlyunderthemeasuredconditions,butalsosharearegulatorystructurethatmayexplaintheircommonregulation.Wedemonstratetheutilityofthisapproachonamicroarraydatasetofyeastgrownunderdifferentnutrientandoxygenlimitations.Ourintegratedclusteringmethodnotonlyunravelsmanyregulatorymodulesthatareconsistentwithcurrentbiologicalknowledge,butalsoprovidesamoreprofoundunderstandingoftheunderlyingprocess.Theaddedvalueofourapproach,comparedwiththeclusteringsolelybasedongeneexpression,isitsabilitytouncoverclustersofgenesthatareinvolvedinmorespecificbiologicalprocessesandareevidentlyregulatedbyasetoftranscriptionfactors.