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Mouse ooplasm confers context-specific reprogramming capacity


Enucleated oocytes have the distinctive ability to reprogram somatic nuclei back to totipotency. Here, we investigate genome-scale DNA methylation patterns after nuclear transfer and compare them to the dynamics at fertilization. We identify specific targets for DNA demethylation after nuclear transfer, such as germline-associated promoters, as well as unique limitations that include certain repetitive element classes.

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Figure 1: Classifying common and unique DNA methylation dynamics during fertilization and nuclear transfer.
Figure 2: Promoter dynamics during SCNT include demethylation of gamete-specific genes.

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We would like to thank all the members of the Meissner and Regev laboratories. We thank M. Garber, N. Yosef, J. Ye, R. Koche, H. Gu, A. Gnirke and T. Mikkelsen for technical advice and discussion and all members of the Broad Sequencing Platform, in particular, F. Kelley, J. Meldrim, T. Fennel, K. Tibbetts and J. Fostel. We also thank S. Levine, M. Gravina and K. Thai from the MIT BioMicro Center. D.E. is supported by the New York Stem Cell Foundation (NYSCF). A.R. is an investigator of the Merkin Foundation for Stem Cell Research at the Broad Institute and is supported by a US National Institutes of Health (NIH) Pioneer Award (5DP1OD003958), a National Human Genome Research Institute (NHGRI) Centers of Excellence in Genomic Science (CEGS) grant (1P50HG006193), the Burroughs Wellcome Career Award at the Scientific Interface and the Howard Hughes Medical Institute (HHMI). A.M. is supported by the Pew Charitable Trusts, the Human Frontiers Science Program and the NIH (U01ES017155, P01GM099117 and 1P50HG006193).

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M.M.C., Z.D.S., D.E. and A.M. conceived and designed the study. D.E. performed SCNT, Z.D.S. performed methylation profiling, and M.M.C. performed all analysis. M.M.C., Z.D.S., A.R. and A.M. interpreted the data. M.M.C., Z.D.S. and A.M. wrote the manuscript with input from the other authors.

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Correspondence to Alexander Meissner.

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Chan, M., Smith, Z., Egli, D. et al. Mouse ooplasm confers context-specific reprogramming capacity. Nat Genet 44, 978–980 (2012).

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