DEGREE OF METHYLATION OF TRANSGENES IS DEPENDENT ON GAMETE OF ORIGIN
DEGREE OF METHYLATION OF TRANSGENES IS DEPENDENT ON GAMETE OF ORIGIN
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DOI：
10.1038/328251a0
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发表时间：
1987-07-16
期刊：
影响因子：
64.8
通讯作者：
BALLING, R
中科院分区：
文献类型：
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作者：
SAPIENZA, C;PETERSON, AC;BALLING, R
来自原核移植实验和经典遗传实验的数据表明，母本和父本遗传对哺乳动物受精卵核的贡献在后续发育过程中的功能并不相同1-5。这些观察结果被解释为雄性和雌性配子发生期间差异“基因组印记”的结果2,3。负责基因组印记的分子机制尚不清楚，但迄今为止收集的数据要求该机制至少满足四个标准：（1）印记必须与原核物理连接2,3； (2) 印记必须在 DNA 复制和细胞分裂中持续存在； (3) 该机制必须能够影响基因表达2,7； (4) 该机制必须能够在连续的世代中将印记的身份从一种性别切换到另一种性别2,3。可以满足前三个标准的一种分子机制是配子发生本身6,8期间或胚胎发生期间合子核形成之前的差异DNA甲基化。我们提供的数据表明，转基因小鼠中外源DNA序列的甲基化模式可以通过在连续几代中改变其配子起源来改变。这些数据表明DNA甲基化也可以满足印记机制的第四个标准。
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.