12.植物表观遗传

PlantEpigeneticsGregorMendel(1822-1884)FatherofGenetics,discoveredthebasiclawsofheredity.ThomasHuntMorgan(1966-1945)Discoveredthe3rdbasicgeneticlaw,togetherwithMendel’stwolaws,theyformthebasisofwhatisnowknownasclassicalgenetics.Elucidationofthe“doublehelixstructure”ofDNAmoleculeisoneofthemostimportantscientificdiscoveryinthe20thcentury,whichsymbolsthebirthofMolecularGenetics.JamesWatson&FrancisCrickMendelianGeneticsAlterationingeneexpressionand/orfunctionNovelphenotypeChangeinnucleotidesequenceMonozygoustwinsshareacommongenotypeandaregeneticallyidenticalThereissignificantphenotypicdiscordance:MentaldisordersCancerDNAIsNotDestinyThecellsaregeneticallyidentical,butdifferent!Whatisepigenetics?*Thesechangesmayremainthroughcelldivisionsfortheremainderofthecell'slifeandmayalsolastformultiplegenerations.*EpigenomeprovidesinstructionsandregulatesthefunctionalaspectsofallthegenesAllheritablechangesingeneexpressionandchromatinorganizationthatareindependentoftheDNAsequenceitself.•Developmentanddifferentiation•Maintenanceofcellularidentity*‘On’or‘over’thegeneticinformationencodedintheDNAEpigeneticsvsGeneticsComponentsA:Nucleosome*Position*Chromatinaccessibility*HigherorderchromatininteractionsB:HistonemodificationsC:DNAmethylationD:Non-codingRNA(e.g.microRNA)CH»CH3CH3NH3H2AH2BH4NNucleosomepositioningHistonevariantdepositionDNAmethylationHistonemodification&recognitionNoncodingRNAEpigeneticinformationsChromosomesconsistofheterochromatinandeuchromatinDenselypackagedheterochromatinLessdenselypackagedeuchromatinDNAaroundthecentromereisusuallypackagedasheterochromatin.CENTROMEREEffectsonreplication,recombination,repair,andtranscriptionDNAmethylationInestablishingheterochromatin,whichisthedrivingforce–DNAmethylation?-Histonemodification?Nucleosome•Locationofanucleosome•Multipleisoformsofthehistones•CovalenthistonemodificationsWherearethenucleosomesinplants?Nucleosomeoccupancyandpositioningarecriticaltobiologicaloutcomes,primarilybecausenucleosomesinhibittheaccessofotherDNA-bindingproteinstoDNA.CanonicalhistonesandhistonevariantsMechanismexistto“openup”chromatinChromatinremodeling,histonemodificationsMechanismexistto“condense”chromatinHistonemodifications,DNAmethylation,chromatinbindingproteinsCanaltergeneactivitywithoutchangeinDNARegulatoryrolesofchromatinifyes:EPIGENETICREGULATIONifno:CHROMATINREGULATIONIsittheexistingchromatinstateheritable?Chromatin-basedrestrictionofgenomeaccessibilityduringdifferentiationSelectiveactivationofgenomeafterperceptionofstimulus(influenceofenvironment/stress)Mitoticmaintenanceofcellidentity(orlossthereofincancer)Dosagecompensationinthemaleversusfemalegenome(Xinactivationinmammals)Memory,Behavior,AgingEpigenetic/chromatinphenomenaDNaseHypersensitive(HS)Mapping•DNaserandomlycutsgenome(moreofteninopenchromatinregion)•Selectshortfragments(twonearbycuts)tosequence•MaptoactivepromotersandenhancersLingetal,MCB2010DHSPeaksCaptureMostTFBindingSites•MotifoccurrenceintheDHSpeakssuggestTFbinding•QuantitativesignalstrengthalsosuggestbindingstabilityThurmanetal,Nat2012Histonepost-translationalmodificationsH2AH2BH3H4HistonemodificationsinArabidopsisHistonelysinescanbereversiblymono-,di-andtrimethylatedHKMT:histonelysinemethyltransferaseHDM:histonedemethylasesMolecularMechanisms–histonemodifications•Modificationsofresiduesinthehistone‘tails’•40possiblemodifications•Modificationalter3-DstructureandmakeDNAmore,orless,accessible•AcetylationfoundinregionsofincreasedgeneexpressionDNA-methylationandchromatininteract–differentialrecruitmentofhistonesHistonemodification&transcriptionH3K27me3isrequiredfortissue-specificgenerepression–Tissue-specificofH3K27me3atafewknowngenesanti-correlatedwithexpressionlevelZhangetal.,2007H3K4me3/H3K4me2H3K4me1H3K36me3H3K36me2H3K36me1ActivationRepressionH3K27me3PromotorRepressedGenePromotorActiveGeneH3K23acH4k8acH4k12acH4K16ac•Chromatinmodificationsarerequiredfortheproperexpressionofconstitutivelyexpressedordevelopmentallyregulatedgenes–Developmentalabnormalitiesinmanychromatinmodificationmutants–Developmentallyregulatedgenesareassociatedwithdifferentmodificationsdependingonwhethertheyare“on”or“off”MolecularMechanisms–DNAmethylation•DNAsequencemadeupof4chemicalbases;adenosine,guanine,tyrosineandcytosine(A,G,T,C)•Onebase,cytosineisepigeneticallymodifiedbyDNAmethylation•EncodedDNAinformation(i.e.‘C’)remainsthesame•Epigeneticcodehaschanged…•DNAmethylationgenerally=suppressionofgeneactivityWhatareimportantfuturetopicsinthefield?2.UnderstandthecomplexrelationshipofDNAmethylationwithotherepigeneticmarks.3.WhataretheintrinsicandenvironmentalfactorsthatinducechangesinDNAmethylationpatterns?1.UnderstandtheevolutionarysignificanceofDNAmethylation.MethylationChangesDuringDevelopmentPaulaVertino,HenryStewartTalksInheritanceofDNAMethylationFromTingWang,WashUNaturalRolesofDNAMethylationinMammalianSystemImprintingXchromosomeinactivationHeterochromatinmaintenanceDevelopmentalcontrolsTissuespecificexpressioncontrolsThreetypesofDNAmethylationinplants•MET1-maintenanceofCGmethylation•CMT3-mainte