简介:探索真核细胞的抄写因素(TF)的性质有约束力的地点并且决定他们怎么不同于包围DNA序列,我们检验了与DNA有约束力的地点联系的四个特征:G+C内容,模式复杂性,palindromic结构,和Markov定序订。我们规章的主题的分析从TRANSFAC数据库获得了,用酵母内部是的遗传因子的序列背景,表明这四个特征在主题序列显示出可变丰富。例如,主题序列比是背景序列是更可能的有palindromic结构。另外,这些特征对规章的主题紧局部性,显示他们自己是主题序列的一个性质并且没被一般倡导者分享规章的主题在住的“环境”。由根据他们绑在的TF班毁坏主题序列,更特定的协会被识别。最后,当其它例如复杂性丰富,越过检验的种类是通用的时,我们发现一些关联例如G+C内容丰富,是种类特定的。这里提供的定量分析应该增加我们protein-DNA相互作用的理解并且也帮助通过生物信息学便于规章的主题的发现。
简介:Despitethefactthatironisoneofthemostabundantelementsoftheearth'scrust,irondeficienciesareseriousproblemsbothinhumannutrition[1]andinagriculture[2].Sixtoeightpercentoftheworld'spopulationispotentiallyaffectedbyirondeficiencyinducedanemia,aleadingcauseofmaternaldeathinAfricanandAsiancountrieswherepeoplerelymostlyonplantsfortheirdailyintakeofiron.Ironcanalsobealimitingfactorinthegrowthofeconomicallyimportantcropplantsbecauseofinadequatesoilchemistry,andsuchdeficienciescannoteasilybecorrectedbyamendingthesoil.Improvingtheplant'sabilitytoabsorbironinadverseconditionsandtoincreasetheiroverallcontentcouldoffersolutionstothesedramaticproblems.Thereforeunderstandingthemolecularmechanismsregulatingironuptakeandhomeostasisinplantshaspotentiallyimportantpracticalapplicationsbothinagricultureandhumanhealth[3].
简介:ThemolecularmechanismsforNF-κBsignalingtransductionandtranscriptionhavebeenthemostattractivesubjectsforbothbasicresearchandpharmaceuticalindustriesduetoitsimportantrolesinbothphysiologicalandpathogenesis,particularlythecloseassociationofdysregulatedNF-κBwithtumorgenesisandinflammation.SeveralnovelintracellularmoleculareventsthatregulateNF-κBactivityhavebeendescribedrecently,includingthediscoveryofanalternativesignalingpathwaythatappearsinducingaspecificsubsetgenesinvolvedinadoptiveimmuneresponse.Multi-levelandmulti-dimensionalregulationofNF-κBactivitybyphosphorylationandacetylationmodificationshaveunveiledandbecamethehottesttargetsforpotentiallytissuespecificmolecularinterventions.AnotheremergingmechanismforNF-κB-responsivegene'sregulationwhereNF-κBparticipatesthetranscriptionalregulationindependentofitscognateregulatorybindingsitewithinthetargetgene'spromoterbutfacilitatingthetransactionactivityofotherinvolvedtranscriptionfactors,thatimplicatedannoveltranscriptionalactivitiesforNF-κB.Thus,thecurrentreviewwillfocusontheserecentprogressesthathavebeenmadeonNF-κBsignalingtransductionandtranscription.Cellular&MolecularImmunology.2004;1(6):425-435.
简介:AbstractObjective:To investigate the roles of transcription factors (TFs) in the etiology of complex human birth defects, including neural tube defects (NTDs), congenital heart diseases (CHDs), and hypospadias.Methods:We examined the overlap of genetically associated genes among NTDs, CHDs, and hypospadias. We then compared the expression profiles of these diseases based on all the detected genes and disease-associated TFs. The differentially expressed TFs that we obtained were further subjected to functional enrichment analysis to elucidate their role in the development of these birth defects.Results:TF genes were significantly enriched in complex birth defects (P= 5.95 × 10-24). NTDs, CHDs, and hypospadias showed distinct gene expression profiles compared with the controls. Although TFs could not efficiently separate CHDs from normal subjects, distinct gene expression profiles of TFs could distinguish NTDs and hypospadias from controls. Differentially expressed TFs can be used to characterize NTDs, hypospadias, and controls. The enriched TFs in biological processes (BPs) reflected the different morphological processes of NTDs, CHDs, and hypospadias.Conclusions:This study indicates that abnormal expression patterns of specific TFs may disrupt the normal requirements for developmental equilibrium through the related BPs. The investigation of genetically associated genes and gene expression profiles for the three different complex birth defects provides new insights into how the dysregulation of TFs influences their developmental process.
简介:MolecularmechanismsoftheKru?ppel-likefamilyoftranscriptionfactors(KLFs)havebeenstudiedmoreinproliferatingcellsthaninpost-mitoticcellssuchasneurons.WerecentlyfoundthatKLFsregulateintrinsicaxongrowthabilityincentralnervoussystem(CNS)neuronsincludingretinalganglioncells,andhippocampalandcorticalneurons.Withatleast15of17KLFfamilymembersexpressedinneuronsandatleast5structurallyuniquesubfamilies,itisimportanttodeterminehowthiscomplexfamilyfunctionsinneuronstoregulatetheintricategeneticprogramsofaxongrowthandregeneration.BycharacterizingthemolecularmechanismsoftheKLFfamilyinthenervoussystem,includingbindingpartnersandgenetargets,andcomparingthemtodefinedmechanismsdefinedoutsidethenervoussystem,wemaybetterunderstandhowKLFsregulateneuritegrowthandaxonregeneration.
简介:Cytokineslikeinterferons(IFNs)playacentralroleinregulatinginnateandspecificimmunitiesagainstthepathogensandneoplasticcells.AnumberofsignalingpathwaysareinducedinresponsetoIFNinvariouscells.OneclassicmechanismemployedbyIFNsistheJAK-STATsignalingpathwayforinducingcellularresponses.Herewedescribethenon-STATpathwaysthatparticipateinIFN-inducedresponses.Inparticular,wewillfocusontheroleplayedbytranscriptionfactorC/EBP-βinmediatingtheseresponses.
简介:RecentinsituhybridizationstudiesshowedthatmRNAlevelsofOLIGlandOLIG2transcriptionfactorsareelevatedinoligodendrogliomas.Weraisedpolyclonalantibodiesagainstasyntheticpeptidehomologoustothehumantran-scriptionfactorOliglandstudiedbyimmunohistochemistrytheexpressionofOliglin84braintumorsandinnon-neoplasticbraintissues.Alloligodendrogliomas,oligoastrocytomas,anddysembryoplasticneuroepithelialtumorsshowedmoderatetostrongintranuclearimmunoreactivityincellsmorphologicallyidentifiedasoligodendrocytes.In
简介:Mammaliancelltotipotencyisasubjectthathasfascinatedscientistsforgenerations.AlonglastingquestionwhethersomeofthesomaticcellsretainstotipotencywasansweredbythecloningofDollyattheendofthe20thcentury.Thedawnofthe218thasbroughtforwardgreatexpectationsinharnessingthepoweroftotipotentcyinmedicine.Throughstemcellbiology,itispossibletogenerateanypartsofthehumanbodybystemcellengineering.Considerableresourceswillbedevotedtoharnesstheuntappedpotentialsofstemcellsintheforeseeablefuturewhichmaytransformmedicineasweknowtoday.Atthemolecularlevel,totipotencyhasbeenlinkedtoasingulartranscriptionfactoranditsexpressionappearstodefinewhetheracellshouldbetotipotent.NamedOct4,itcanactivateorrepresstheexpressionofvariousgenes.Curiously,verylittleisknownaboutOct4beyonditsabilitytoregulategeneexpression.ThemechanismbywhichOct4specifiestotipotencyremainsentirelyunresolved.Inthisreview,wesummarizerethestructureandfunctionofOct4andaddresstoOct4functioninmaintainingtotipotencyorpluripotencyofembryonicstemcels.
简介:Mammaliantoothdevelopmentislargelydependentonsequentialandreciprocalepithelial-mesenchymalinteractions.Theseprocessesinvolveaseriesofinductiveandpermissiveinteractionsthatresultinthedetermination,differentiation,andorganizationofodontogenictissues.Multiplesignalingmolecules,includingBMPs,FGFs,Shh,andWntproteins,havebeenimplicatedinmediatingthesetissueinteractions.Transcriptionfactorsparticipateinepithelial-mesenchymalinteractionsvialinkingthesignalingloopsbetweentissuelayersbyrespondingtoinductivesignalsandregulatingtheexpressionofothersignalingmolecules.Adultstemcellsarehighlyplasticandmultipotent.Thesecellsincludingdentalpulpstemcellsandbonemarrowstromalcellscouldbereprogrammedintoodontogenicfateandparticipatedintoothformation.Recentprogressinthestudiesofmolecularbasisoftoothdevelopment,adultstemcellbiology,andregenerationwillprovidefundamentalknowledgefortherealizationofhumantoothregenerationinthenearfuture.
简介:抄写开始地点(TSS)区域与另外的倡导者元素相比显示出更大的可变性。我们被感兴趣由把信息内容用作一项措施寻找它的可变性。我们在这研究注意可变性在与15nt的块相比包围TSS区域的5核苷酸(nt)的块是重要的。这建议可以被包含的实际区域在在尺寸的5-10nt的范围。为Escherichia关口i,我们注意从dinucleotide替换矩阵的信息内容清楚地显示出更好的辨别,建议一些关联的存在。然而,为人,这效果是少得多,并且为老鼠,它实际上是不在的。我们能断定存在短期在TSS区域以内的关联是种类依赖者并且不是通用的。我们进一步观察到在除了TSS的mitochondrial控制元素有另外的可变区域。有效比较能仅仅在块上被做,这也被注意,当单个核苷酸比较不给我们任何可检测的信号时。
简介:AbstractBackground:Glioma is a common malignant brain tumor. The purpose of this study was to investigate the role of the transcription factor SPI1 in glioma.Methods:SPI1 expression in glioma was identified using qRT-PCR and Western blotting. Cell proliferation was assessed using the CCK8 assay. Transwell and wound healing assays were utilized to evaluate cell migration. Additionally, cell cycle and apoptosis were detected using flow cytometry.Results:We observed that the expression level of SPI1 was up-regulated in glioma tissues, compared to normal tissues. Furthermore, we found that SPI1 is able to promote proliferation and migration of glioma cells in vitro. Flow cytometry results demonstrate that, compared to si-NC cells, si-SPI1 cells stagnated in the G1 phase, and downregulation of SPI1 expression is able to increase rates of apoptosis. Double luciferase activity and chromatin immunoprecipitation assay results indicated that SPI1 can bind to the promoter sites and promote the proliferation and migration of glioma cells by regulating the expression of oncogenic PAICS.Conclusions:Our results suggest that SPI1 can promote proliferation and migration of glioma. Furthermore, SPI1 can be utilized as a potential diagnostic marker and therapeutic target for glioma.
简介:Toelucidatethemechanismofphotodynamicdamageofcells,theeffectofHPDpluslightontranscriptlonalectlvltyInthemucleusIsolatefromthenormalratliverwasstudiedinvitorby3H-UTPincorporationintoRNA.MeasurementsoffluorescencespectrumshowedthatHPDwasboundtothenucleusanditsfluorescenceIntensityIncreasedwiththeIncreaseofHPDconcentration.TheexperimentalresultsIndicatedthatnochangescouldbeobservedwheneitherHPDorlightwasusedalone.WhereasthenucleartranscriptionactivitywasfoundtobeinhibitedsignificantlybybothHPDandlighttreatment,andthedegreeofInhibitionwasdependentontheHPDconcentrationandthetimeofexposuretolight.Aftertreatmentby3μg/mlHPD,theinhibitionrateofthenucleartranscriptionactivitywas23%,45%,69%,80%and90%,respectivelyforlightexposureof2,5,10,20and30minutes.Ourresultssuggestedthatdose-dependentdecreasesinthenucleartranscriptionactivity,andmarkedinhibitionofthe
简介:HELcells,ahumanerythroleukemiacellline,mainlyexpressthefetal(γ)globingeneandtraceamountoftheembryonic(ε)globingene,butnotadult(β)globingene.Hereweshowthathydroxyurea(HU)caninduceHELcellstoexpressadult(β)globingeneandleadthesecellstoterminaldifferentiation.ResultsshowedinGelmobilityshiftassaysthatGATAfactorscouldspecificallybindtotheregulatoryelementsofhumanβ-globingene,includingtheproximalregulatoryelement(theβ-promoter)andthedistalregulatoryelements(theDNaseIhypersensitivesitesintheLCR,HS2-HS4coresequences).However,theDNAbindingpatternsofGATAfactorswerequitedifferentbetweenHU-inducedanduninducedHELcells.Western-blotanalysisofnuclearextractsfromboththeuninducedandHU-inducedHELcellsrevealedthatthelevelofGATA-2transcriptionfactordecreased,whereasthelevelofGATA-1transcriptionfactorincreasedfollowingthetimeofhydroxyureainduction.Furthermore,usingRT-PCRanalysistheexpressionofhumanβ-globingeneinHU-inducedHELcellscouldbeblockedagainwhenHELcellswereincubatedinthepresenceofantisenseoligonucleotidesforhGATA-1,suggestingthattheupregulationofhGATA-1transcriptionfactormightbecriticalfortheexpressionofhumanβ-globingeneinHU-inducedHELcells.
简介:Inordertostudythefunctionalstructureofthetranscriptionterminatorsandthemechanismoftemination,asurveyofthechromatinstructure,includingthelocationofDNaseIhypersensitivesitesandthenucleosomearrangement,ofyeastADH1andFLPterminatorswasmade.TheresultsshowthatthereisnorelationshipbetweenthefunctionoftheterminatorsandtheexistenceofDNaseIhypersensitivesites.However,itisfoundthatthereisalwaysanucleosmoeattheimmediateupstreamofthetranscriptionalterminationsites.Asacontrol,thechromatinstructuresofthepBR322DNAfragmentsontheyeastshuttervectorsarealsoinvestigatedatthesametime.TherandomnucleosomearrangementonthebacterialDNAinyesastagreeswiththepublishedreports.Anewhypothesis,aboutthemechanismoftranscriptionalterminationisputforwardandthereasonofdifferentnucleosomearrengementontheDNAswhichareoriginallyfromdifferentspeciesinyeastisdiscussed.
简介:组蛋白deacetylases(HDAC)并且嘘一乙酰转移ases(帽子)是其酶的活动控制蛋白质离氨酸残余的乙酰化状态的二抵抗酶家庭,尤其是在核心histones.Acetylation的N终端扩展包含的那些嘘通过它对染色质符合构造的影响影响基因表示。Inaddition,几non-histone蛋白质由特定的离氨酸残余的乙酰化状态在他们的稳定性或生物功能被调整。HDAC在大量的生物学过程干涉并且是部分一多每个成员在有它的专业化功能的蛋白质家庭。另外,HDAC活动紧通过指向的招募,protein-proteininteractions和translational以后修正被控制。房间周期前进,房间幸存和区别的控制在这些酶的最重要的角色之中。因为这些过程被恶意的转变影响,HDAC禁止者作为反被开发在癌症病人的肿瘤的药和areshowing鼓励功效。
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.