Abstract
In mammals, epigenetic marks on the X chromosomes are involved in dosage compensation. Specifically, they are required for X chromosome inactivation (XCI), the random transcriptional silencing of one of the two X chromosomes in female cells during late blastocyst development1,2,3,4,5,6,7,8. During natural reproduction, both X chromosomes are active in the female zygote2. In somatic-cell cloning, however, the cloned embryos receive one active (Xa) and one inactive (Xi) X chromosome from the donor cells. Patterns of XCIhave been reported normal in cloned mice9, but have yet to be investigated in other species. We examined allele-specific expression of the X-linked monoamine oxidase type A (MAOA) gene and the expression of nine additional X-linked genes in nine cloned XX calves. We found aberrant expression patterns in nine of ten X-linked genes and hypomethylation of Xist in organs of deceased clones. Analysis of MAOA expression in bovine placentae from natural reproduction revealed imprinted XCI with preferential inactivation of the paternal X chromosome. In contrast, we found random XCI in placentae of the deceased clones but completely skewed XCI in that of live clones. Thus, incomplete nuclear reprogramming may generate abnormal epigenetic marks on the X chromosomes of cloned cattle, affecting both random and imprinted XCI.
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Acknowledgements
The authors are indebted to H. Lewin and M. Band for providing primers for the bovine X-linked genes, to B. Jeong for initiating cell cultures, to R. Foote and M. Julian for critical reading of the manuscript and to J. Xu, B. Enright, S. Chaubal and J. Slisz for sample collection. This project was supported by grants from the National Institutes of Health, United States Department of Agriculture and Connecticut Innovations (to X.Y. and X.T.) and from Conselho Nacional ed Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado de São Paulo (to L.V.P.). This manuscript is a scientific contribution of the Storrs Agricultural Experiment Station at the University of Connecticut.
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Xue, F., Tian, X., Du, F. et al. Aberrant patterns of X chromosome inactivation in bovine clones. Nat Genet 31, 216–220 (2002). https://doi.org/10.1038/ng900
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DOI: https://doi.org/10.1038/ng900
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