title: Single-cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos.
abstract: Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of the experimental inaccessibility of early-stage embryos. Here, we introduce a methodologic advance, probing single cells for various DNA-methylation errors at multiple loci, to reveal failed maintenance of epigenetic mark results in chimeric mice, which display unpredictable phenotypes leading to developmental arrest. Yet we show that mouse pronuclear transfer can be used to ameliorate such reprogramming defects. This study not only details the epigenetic reprogramming dynamics in early mammalian embryos but also suggests diagnostic and potential future therapeutic applications.
authors.affiliation: Mammalian Development Group, Institute of Medical Biology, A*STAR, Singapore.
authors.forename: Chanchao
authors.initials: C
authors.lastname: Lorthongpanich
authors.forename: Lih Feng
authors.initials: LF
authors.lastname: Cheow
authors.forename: Sathish
authors.initials: S
authors.lastname: Balu
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Knowles
authors.forename: William F
authors.initials: WF
authors.lastname: Burkholder
authors.forename: Davor
authors.initials: D
authors.lastname: Solter
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Messerschmidt
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D065150:Cellular Reprogramming / Q000235:genetics*; D046528:Chimerism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D059010:Single-Cell Analysis; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D009687:Nuclear Proteins; D012097:Repressor Proteins; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28