Joint Binding of OTX2 and MYC in Promotor Regions Is Associated with High Gene Expression in Medulloblastoma 英文参考文献.docVIP

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Joint Binding of OTX2 and MYC in Promotor Regions Is Associated with High Gene Expression in Medulloblastoma 英文参考文献.doc

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Joint Binding of OTX2 and MYC in Promotor Regions Is Associated with High Gene Expression in Medulloblastoma 英文参考文献

JointBindingofOTX2andMYCinPromotorRegionsIs AssociatedwithHighGeneExpressionin Medulloblastoma JensBunt,NancyE.Hasselt,DannyA.Zwijnenburg,JanKoster,RogierVersteeg,MarcelKool*¤ DepartmentofOncogenomics,AcademicMedicalCenter,Amsterdam,TheNetherlands Abstract BothOTX2andMYCareimportantoncogenesinmedulloblastoma,themostcommonmalignantbraintumorinchildhood. MuchisknownaboutMYCbindingtopromoterregions,butOTX2bindingishardlyinvestigated.WeusedChIP-on-chip datatoanalyzethebindingpatternsofbothtranscriptionfactorsinD425medulloblastomacells.Whencombiningthedata for all promoter regions in the genome, OTX2 binding showed a remarkable bi-modal distribution pattern with peaks around2250bpupstreamand+650bpdownstreamofthetranscriptionstartsites(TSSs).Indeed,40.2%ofallOTX2-bound TSSshadmorethanonesignificantOTX2-bindingpeak.ThisOTX2-bindingpatternwasverydifferentfromtheTSS-centered single peak binding pattern observed for MYC and other known transcription factors. However, in individual promoter regions,OTX2andMYChaveastrongtendencytobindinproximityofeachother.OTX2-bindingsequencesaredepleted nearTSSsinthegenome,providinganexplanationfortheobservedbi-modaldistributionofOTX2binding.Thiscontrasts totheenrichment ofE-box sequences atTSSs. BothOTX2andMYC bindingindependently correlated with higher gene expression. Interestingly, genes of promoter regions with multiple OTX2 binding as well as MYC binding showed the highestexpressionlevelsinD425cellsandinprimarymedulloblastomas.Geneswithinthisclassofpromoterregionswere enrichedformedulloblastomaandstemcellspecificgenes.Ourdatasuggestanimportantfunctionalinteractionbetween OTX2andMYCinregulatinggeneexpressioninmedulloblastoma. Citation:BuntJ,HasseltNE,ZwijnenburgDA,KosterJ,VersteegR,etal.(2011)JointBindingofOTX2andMYCinPromotorRegionsIsAssociatedwithHighGene ExpressioninMedulloblastoma.PLoSONE6(10):e26058.doi:10.1371/journal.pone.0026058 Editor:ElianaSaulFurquimWerneckAbdelhay,InstitutoNacionaldeCa?ncer, Brazil ReceivedSeptember2