Dynamic Reprogramming of DNA Methylation in the Early Mouse Embryo

Developmental Biology

Fátima Santos¹  Brian Hendrich¹  Wendy Dean¹  Wolf Reik¹ 

[1] Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Programme, The Babraham Institute, Cambridge, CB2 4AT, United Kingdom

关键词: demethylation;    active;    passive;    paternal;    maternal resistance;    epigenetic;    mouse;   

DOI  :  10.1006/dbio.2001.0501

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Dynamicepigeneticmodificationofthegenomeoccursduringearlydevelopmentofthemouse.Activedemethylationofthepaternalgenomeoccursinthezygote,followedbypassivedemethylationduringcleavagestages,anddenovomethylation,whichisthoughttohappenafterimplantation.Wehaveinvestigatedtheseprocessesbyusingindirectimmunofluoresencewithanantibodyto5-methylcytosine.Incontrasttopreviouswork,weshowthatdemethylationofthemalepronucleusiscompletedwithin4hoffertilisation.Thisactivityisintricatelylinkedwithandnotseparablefrompronucleusformation.Inconditionspermissiveforpolyspermy,uptofivemalepronucleiunderwentdemethylationinthesameoocyte.PaternaldemethylationinfertilisedoocytesdeficientforMBD2,theonlycandidatedemethylase,occurrednormally.Passivelossofmethylationoccurredinastepwisefashionuptothemorulaestagewithoutanyevidenceofspatialcompartmentalisation.Denovomethylationwasobservedspecificallyintheinnercellmass(ICM)butnotinthetrophectodermoftheblastocystandhencemayhaveanimportantroleinearlylineagespecification.Thisisthefirstcompleteanddetailedanalysisoftheepigeneticreprogrammingcycleduringpreimplantationdevelopment.Thethreephasesofmethylationreprogrammingmayhaverolesinimprinting,thecontrolofgeneexpression,andtheestablishmentofnucleartotipotency.

【 授权许可】

Unknown