Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes.
Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes.
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DOI：
10.1016/j.molcel.2012.07.010
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发表时间：
2012-09-28
期刊：
影响因子：
16
通讯作者：
Bourc'his, Deborah
中科院分区：
文献类型：
--
作者：
Proudhon, Charlotte;Duffie, Rachel;Ajjan, Sophie;Cowley, Michael;Iranzo, Julian;Carbajosa, Guillermo;Saadeh, Heba;Holland, Michelle L.;Oakey, Rebecca J.;Rakyan, Vardhman K.;Schulz, Reiner;Bourc'his, Deborah
确定基因座与父母的DNA甲基化差异是解开父母的起源表型的关键。通过在无母体甲基化的着床后小鼠胚胎（Dnmt 3L-/+）中进行MeDIP-Seq筛选，我们证明了在妊娠中期几乎不存在母体特异性甲基化。我们揭示了两种形式的卵母细胞特异性甲基化遗传：局限于植入前，或具有较长的持续时间，即母系印记位点。瞬时和印记的母系生殖系DMR（gDMR）在配子和植入前胚胎中是不可区分的，然而，在植入时父系等位基因的从头甲基化描绘了它们的命运，并作为父母遗传差异的主要平衡因素。我们的特点是两个新的印迹gDMR，在Cdh 15和AK 008011位点，与组织特异性印迹损失，再次通过父系甲基化增益。保护受精后去甲基化已被强调为有助于维持从配子遗传的亲本起源甲基化。在这里，我们提供的证据表明，防止从头甲基化作为一个平等的主要支点，在植入和整个生命。哺乳动物中很少有亲本特异性甲基化标记的终身维持，从头甲基化是亲本遗传差异的主要平衡因素，印迹甲基化标记可以以组织特异性方式存在，很可能很少有新的印迹基因座有待发现。
Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life. ► Lifelong maintenance of parent-specific methylation marks is rare in mammals ► De novo methylation acts as a major leveling factor of parent-inherited differences ► Imprinted methylation marks can exist in a tissue-specific manner ► It is very likely that very few new imprinted loci remain to be discovered
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