A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints.

A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints.
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DOI:
10.1016/j.devcel.2008.08.014
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发表时间:
2008-10
期刊:
影响因子:
11.8
通讯作者:
Ferguson-Smith, Anne C.
Ferguson-Smith, Anne C.
中科院分区:
生物学1区
文献类型:
--
作者:
Li, Xiajun;Ito, Mitsuteru;Zhou, Fen;Youngson, Neil;Zuo, Xiaopan;Leder, Philip;Ferguson-Smith, Anne C.

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负责维持小鼠胚胎中基因组甲基化印记的机制尚不清楚。我们在编码KRAB锌指蛋白的Zfp57基因座中产生敲除小鼠。Zfp57合子功能的缺失导致部分新生儿致死,而消除Zfp57的母体和合子功能导致高度外显的胚胎致死。在卵母细胞中,Zfp57的缺失导致在Snrpn印迹区域不能建立母体甲基化印迹。有趣的是,当合子Zfp57存在于胚胎中时,甲基化印记特异性地在母体来源的Snrpn印记区域重新获得。这表明基因组印记可能存在DNA甲基化无关的记忆。Zfp57也是受精后维持多个印记结构域的母本和父本甲基化印记所必需的。对基因组印记的影响与Zfp57突变体的母合子致死性一致。
The mechanisms responsible for maintaining genomic methylation imprints in mouse embryos are not understood. We generated a knockout mouse in the Zfp57 locus encoding a KRAB zinc finger protein. Loss of just the zygotic function of Zfp57 causes partial neonatal lethality, while eliminating both maternal and zygotic functions of Zfp57 results in a highly penetrant embryonic lethality. In oocytes, absence of Zfp57 results in failure to establish maternal methylation imprints at the Snrpn imprinted region. Intriguingly, methylation imprints are re-acquired specifically at the maternally derived Snrpn imprinted region when the zygotic Zfp57 is present in embryos. This suggests that there may be DNA methylation-independent memory for genomic imprints. Zfp57 is also required for the post-fertilization maintenance of maternal and paternal methylation imprints at multiple imprinted domains. The effects on genomic imprinting are consistent with the maternal-zygotic lethality of Zfp57 mutants.
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