Report

Single-Cell DNA-Methylation Analysis Reveals Epigenetic Chimerism in Preimplantation Embryos

See allHide authors and affiliations

Science  06 Sep 2013:
Vol. 341, Issue 6150, pp. 1110-1112
DOI: 10.1126/science.1240617

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Fatal Chimeras

Impaired DNA-methylation maintenance during early embryonic development may cause imprinting-related diseases. Lorthongpanich et al. (p. 1110) have devised a sensitive assay to probe multiple imprinted gene loci for their DNA-methylation state at the single-cell level. Blastomeres with defective imprinting showed complex, epigenetic chimeras developed with fatal defects. Pronuclear transfer restored normal mouse development, offering a therapeutic strategy to overcome epigenetic defects caused by maternal insufficiencies.

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.

View Full Text

Stay Connected to Science