Publication Date:
2013-09-07
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorthongpanich, Chanchao -- Cheow, Lih Feng -- Balu, Sathish -- Quake, Stephen R -- Knowles, Barbara B -- Burkholder, William F -- Solter, Davor -- Messerschmidt, Daniel M -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 6;341(6150):1110-2. doi: 10.1126/science.1240617.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Mammalian Development Group, Institute of Medical Biology, A*STAR, Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24009393" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Blastocyst/*metabolism
;
Cellular Reprogramming/*genetics
;
*Chimerism
;
*DNA Methylation
;
*Epigenesis, Genetic
;
Gene Deletion
;
*Gene Expression Regulation, Developmental
;
Genetic Loci
;
Humans
;
Mice
;
Mice, Inbred C57BL
;
Mice, Transgenic
;
Nuclear Proteins/genetics
;
Repressor Proteins/genetics
;
Single-Cell Analysis
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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