Caenorhabditis elegans Histone Methyltransferase MET-2 Shields the Male X Chromosome from Checkpoint Machinery and Mediates Meiotic Sex Chromosome Inactivation 英文参考文献.docVIP

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Caenorhabditis elegans Histone Methyltransferase MET-2 Shields the Male X Chromosome from Checkpoint Machinery and Mediates Meiotic Sex Chromosome Inactivation 英文参考文献.doc

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Caenorhabditis elegans Histone Methyltransferase MET-2 Shields the Male X Chromosome from Checkpoint Machinery and Mediates Meiotic Sex Chromosome Inactivation 英文参考文献

CaenorhabditiselegansHistoneMethyltransferaseMET- 2ShieldstheMaleXChromosomefromCheckpoint MachineryandMediatesMeioticSexChromosome Inactivation PaulaM.Checchi,JoAnneEngebrecht* DepartmentofMolecularandCellularBiology,UniversityofCaliforniaDavis,Davis,California,UnitedStatesofAmerica Abstract Meiosisisaspecializedformofcellulardivisionthatresultsintheprecisehalvingofthegenometoproducegametesfor sexualreproduction.Checkpointsfunctionduringmeiosistodetecterrorsandsubsequentlytoactivateasignalingcascade that prevents the formation of aneuploid gametes. Indeed, asynapsis of a homologous chromosome pair elicits a checkpointresponsethatcaninturntriggergermlineapoptosis.Inaheterogameticgermline,however,sexchromosomes proceed through meiosis with unsynapsed regions and are not recognized by checkpoint machinery. We conducted a directedRNAiscreeninCaenorhabditiseleganstoidentifyregulatoryfactorsthatpreventrecognitionofheteromorphicsex chromosomesasunpairedanduncoveredarolefortheSETdomainhistoneH3lysine9histonemethyltransferase(HMTase) MET-2andtwoadditionalHMTasesinshieldingthemaleXfromcheckpointmachinery.WefoundthatMET-2alsomediates the transcriptional silencing program of meiotic sex chromosome inactivation (MSCI) but not meiotic silencing of unsynapsedchromatin(MSUC),suggestingthattheseprocessesaredistinct.Further,MSCIandcheckpointshieldingcanbe uncoupled, as double-strand breaks targeted to an unpaired, transcriptionally silenced extra-chromosomal array induce checkpointactivationingermlinesdepletedformet-2.Insummary,ourdatauncoveramechanismbywhichrepressive chromatin architecture enables checkpoint proteins to distinguish between the partnerless male X chromosome and asynapsedchromosomestherebyshieldingtheloneXfrominappropriateactivationofanapoptoticprogram. Citation:ChecchiPM,EngebrechtJ(2011)CaenorhabditiselegansHistoneMethyltransferaseMET-2ShieldstheMaleXChromosomefromCheckpointMachinery andMediatesMeioticSexChromosomeInactivation.PLoSGenet7(9):e1002267.doi:10.1371/