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  • Epigenetic S

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    youssraselim
    19 tayangan14 halaman
    Heritable traits that do not involve changes to the underlying DNA sequence. Epigenetics can be used to describe any aspect other than DNA sequence that influences the development of an organism. DNA Methylation is the addition of a methyl group (M) to the DNA base cytosine (C) in a DNA methylation.

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    Epigenetic s

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    Heritable traits that do not involve changes to the underlying DNA sequence. Epigenetics can be used to describe any aspect other than DNA sequence that influences the development of an organism. DNA Methylation is the addition of a methyl group (M) to the DNA base cytosine (C) in a DNA methylation.

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    Attribution Non-Commercial (BY-NC)
    Unduh sebagai PDF, TXT atau baca online dari Scribd
    Tandai sebagai konten tidak pantas
    19 tayangan14 halaman

    Epigenetic S

    Diunggah oleh

    youssraselim
    Heritable traits that do not involve changes to the underlying DNA sequence. Epigenetics can be used to describe any aspect other than DNA sequence that influences the development of an organism. DNA Methylation is the addition of a methyl group (M) to the DNA base cytosine (C) in a DNA methylation.

    Hak Cipta:

    Attribution Non-Commercial (BY-NC)
    Unduh sebagai PDF, TXT atau baca online dari Scribd
    Tandai sebagai konten tidak pantas
    dari 14

    5/5/2009

    Epigenetics

    WhatisEpigenetics
    Definition heritabletraitsthatdonotinvolve changestotheunderlyingDNAsequence. h t th d l i DNA Epigenetic canbeusedtodescribeanyaspect otherthanDNAsequencethatinfluencesthe developmentofanorganism.

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    Epigeneticsandtheenvironment

    Genomicvs Epigenomic
    Leadstoproblemsingeneticscreening

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    Typesofepigenetics
    HistoneModifications DNAMethylation MicroRNAs,smallinterferingRNAs,RNA interference Polycomb groupsilencing Hox genes

    euchromatin chromatininamorerelaxed statethatispoisedfortranscription,oris t t th t i i df t i ti i transcriptionactive) heterochromatin highlycondensedchromatin thatistranscriptioninactive


    mitotic&meioticchromosomes mitotic & meiotic chromosomes barbody(condensedXchromosome) centromeres telomeres

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    Histonesmodifiers
    HATcomplexes(histoneacetyltransferases) HDACcomplexes(histonedeacetylases) HDAC complexes (histone deacetylases) HTMcomplexes(histonemethyltransferases) HDMcomplexes(histonedemethylases) histoneser\thr proteinkinases (histonephosphorylation) histoneproteinphosphatases (dephosphorylate histoneser& thr)

    HistoneModifications

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    DefectsinH3,H4modificationscan haveimportantimplicationsinthe development ofvariouscancers becausecorrectregulationof heterochromatinandeuchromatin isdisrupted. Regionsofheterochromatinbecome demethylated andconvertedto euchromatin andregionsof euchromatin becomemethylated whichleadstogene inactivation.

    Whichhistonemodificationismostimportant ingenetranscriptionregulation?

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    DNA Methylation is the addition of a methyl group (M) to the DNA base cytosine (C) in a DNA methylation is the addition ofCpG sequence (M) to the DNA a methyl group DNA methylation y base cytosine i a C G sequence b t i in CpG

    MethylationMutation

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    Imprinting
    Genesexpressionwhichisdictatedby maternalorpaternalDNA. t l t l DNA 50knownimprintedgenes Mostmaternal MostdirectedbyDNAmethylation,someby histonemodification histone modification

    ProblemswithImprinting
    p paternalimprinting,theresultisPraderWilli syndrome p g, y (characterised byhypotonia,obesity,andhypogonadism

    maternalimprinting,theresultisAngelman syndrome (characterised byepilepsy,tremors,andaperpetuallysmiling facialexpression

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    The Process of Methylation

    PronuclearMethylationAfterFertilization

    G1SS

    G2 Green Methylated DNA Red DNA

    Cyclophosphamide treatedmalerats

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    XchromosomeInactivation
    Xic:Xinactivationcontrolcenter(~100kb) Xist andTsix aretranscribedtoyieldnon codingmRNAswhichareantisensetoeach other

    CTCF

    Atfertilization,theXist/Tsix locushasH3K9 onthematernalX At fertili ation the Xist/Tsix locus has H3 K9M on the maternal X chromosome. H3K9methylationkeepsthisregionsilent. PaternalXchromosomeisunmodified,allowingexpressionofXist RNA

    Xist RNA"coats"theparental Xchromosomeincis atXic (viaRNA/DNAbp ?). Xist notexpressedonmaternal Xchromosome. H3K9M hasbeenreplacedbyH3K4M andsubsequentacetylation(H3K9Ac)on thematernal Xchromosome.Thelocusispoised,butnotexpressed.

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    Thematernal Xchromosomenowhasactiveeuchromatin atXist/Tsix locus. ThisallowsbindingofCTCFandTsix transcription.ThisantisenseRNAblocks Xist transcription. maternal XchromosomedoesnotexpressXist ThispreventsXist RNAfromblockingtheXic domainonmaternal Xchromosome. *ResistanceofmaternalXchromosometoinactivationappearstodependon this. H3K273M recruitsasecondremodelingcomplexthatreplacesH2AwithH2A.1 varient,ahistonevarient commonlyfoundinconstitutiveheterochromatin.

    H3K273M isfollowedbyH3K93M andsubsequentcreationofheterochromatinatpaternal Xic domain. HeterochromatinisinitiatedbyXist expression,butisthenpropagatedthroughoutthe parentalXchromosomevianucleosomes whichhaveincorporatedmacroH2A.1andDNA CMpG methylation. Eventuallyalmosttheentirechromosomeistranscriptionaly silenced. **Thisstateistheninheritedepigenetically. Duringlaterdevelopmentalstages,the"embryoproper"differentiatesfromtheinner massoftheblastocyst. Theearlypaternal imprintingprogramislostandXinactivationmustbereset.

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    Summary

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