Abstract
Data derived from both pronuclear transplantation experiments and classical genetic experiments indicate that the maternal and paternal genetic contributions to the mammalian zygote nucleus do not function equivalently during subsequent development1–5. These observations have been interpreted as resulting from differential 'genome imprinting' during male and female gametogenesis2,3. The molecular mechanism responsible for genome imprinting is unknown, but data gathered to date require that the mechanism fulfil at least four criteria: (1) the imprint must be physically linked to the pronucleus2,3; (2) the imprint must persist through DNA replication and cell division6; (3) the mechanism must be capable of affecting gene expression2,7; and (4) the mechanism must be capable of switching the identity of the imprint from one sex to the other in successive generations2,3. One molecular mechanism which could satisfy the first three criteria is differential DNA methylation during gametogenesis itself6,8, or before formation of the zygote nucleus during embry-ogenesis. We present data indicating that the methylation patterns of exogenous DNA sequences in transgenic mice can be changed by switching their gamete of origin in successive generations. These data suggest that DNA methylation can also satisfy the fourth criterion for an imprinting mechanism.
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Sapienza, C., Peterson, A., Rossant, J. et al. Degree of methylation of transgenes is dependent on gamete of origin. Nature 328, 251–254 (1987). https://doi.org/10.1038/328251a0
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DOI: https://doi.org/10.1038/328251a0
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