Single-Cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos
Supplementary materials_Single-cell DNA-methylation analysis reveals epigenetic chimerism in preimplantation embryos (1).pdf (447.0Kb)
Cheow, Lih Feng
Quake, Stephen R.
Knowles, Barbara B.
Burkholder, William F.
Messerschmidt, Daniel M.
Date of Issue2013
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.
© 2013 American Association for the Advancement of Science. This is the author created version of a work that has been peer reviewed and accepted for publication by Science, American Association for the Advancement of Science. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1126/science.1240617].