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Lecture 26 - RNAP1& RNAP2 - BIOL308.pdf

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BIOL 308
Bruce Wolff

Lecture 26Protection of active gene promoters from methylation4Deficiency of CG pairs in genome in general ave 40Mostly present in some promoters CpG boxes or islandsMethyl groups are attached to C in some CG doublets on DNAElimination of methylated C during evolution through conversion into TDeamination of normal C repair system thinks its U not present in DNA mutation is recognized gets repairedDeamination of methylated C repair system thinks its T present in DNA mutation is not recognized for repair it staysMethylation of Cin CpG doublets prevents transcription in generalBoth DNA and histones can be methylated generally a sign of inactive chromatinheterochromatinMethylation affects chromatin structureMethylated CpGs recognize by methylbinding domain proteinsMBP that can recruit histonemodification enzymes such as histone deacetylaseHDAC and histone methyl transferaseHMTHistone deacetylation and methylaton local chromatin will be condensedExtensive methylation near or in a gene sequence generally prevents or stops transcription of that geneCpG islandsin promoters of houskeeping genes are preserved as unmethylated Genes are activeislands stretches of 200500 nucleotides with GC content amount of CpG doublets 50 different definitionsIslands act either as core promoters of upstream elementsHow are the promoters of active genes protected from being methylatedMechanism is still unclearInherent sequence properties prevent binding of DNA methytransferase DNMTaExistence of demthylase DMbGTFs and RNAP II H3 tail modifications exclude the DNMT from sites of transcriptional initiationcThere are no methyl groups on the new DNA strand formed during replication One strand parent is methylated the other is notDemethylase existence is postulated active demethylation is happening as well but the actual enzyme hasnt been foundMaintenance methylase recognized single strand methylation and repairs the other new strand NOTES FROM LECTURES Page 1
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