Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome 英文参考文献.docVIP

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Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome 英文参考文献.doc

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Putative Zinc Finger Protein Binding Sites Are Over-Represented in the Boundaries of Methylation-Resistant CpG Islands in the Human Genome 英文参考文献

PutativeZincFingerProteinBindingSitesAreOver- RepresentedintheBoundariesofMethylation-Resistant CpGIslandsintheHumanGenome ShicaiFan1,3,FangFang1,XuegongZhang1,MichaelQ.Zhang1,2* 1MOEKeyLaboratoryofBioinformaticsandBioinformaticsDivision,TNLIST,DepartmentofAutomation,TsinghuaUniversity,Beijing100084,China, 2Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America, 3School of Automation Engineering, University of ElectronicScienceandTechnologyofChina,Chengdu,China Background.MajorityofCpGdinucleotidesinmammaliangenomestendtoundergoDNAmethylation,butmostCpGislands areresistanttosuchepigeneticmodification.Understandingaboutmechanismsthatmayleadtothemethylationresistanceof CpGislandsisstillverypoor.Methodology/PrincipalFindings.Usingthegenome-scaleinvivoDNAmethylationdatafrom humanbrain,weinvestigatedtheflankingsequencefeaturesofmethylation-resistantCpGislands,anddiscoveredthatthere are several over-represented putative Transcription Factor Binding Sites (TFBSs) in methylation-resistant CpG islands, and aspecificgroupofzincfingerproteinbindingsitesareover-representedinboundaryregions(,400bp)flankingsuchCpG islands.About77%oftheover-representedputativeTFBSsareconservedamonghuman,mouseandrat.Wealsoobservedthe enrichment of 4histone methylations in methylation-resistant CpG islands or theirboundaries. Conclusions/Significance. Our results suggest a possible mechanism that certain putative zinc finger protein binding sites over-represented in the boundary regions of the methylation-resistant CpG islands may block the spreading of methylation into these islands, and those TFBSs over-represented within the islands may both reinforce the methylation blocking and promote transcription. SomehistonemodificationsmayalsoenhancetheimmunityoftheCpGislandsagainstDNAmethylationbyaugmentingthese TFs’ binding. We speculate that the dynamical equilibrium between methylation spreading and blocking is likely to be responsiblefortheestablishmentandmaintenanceo