Tissue-specific regulation of Igf2r/Airn imprinting during gastrulation.
Tissue-specific regulation of Igf2r/Airn imprinting during gastrulation.
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DOI：
10.1186/s13072-015-0003-y
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发表时间：
2015
影响因子：
3.9
通讯作者：
Mager J
中科院分区：
文献类型：
--
作者：
Marcho C;Bevilacqua A;Tremblay KD;Mager J
正常发育需要在谱系分配和组织分化过程中对基因表达进行适当的表观遗传调节。一个例子是基因组印记，它被定义为起源于父母的单等位基因表达。印记的建立很大程度上是由于来自精子和卵子单倍体基因组的受精卵的表观遗传学差异。在小鼠体内，大约有150个已知的印记基因，其中许多出现在一起调节的印记基因簇中。一个印迹簇包括母系表达的Igf2r、slc22a2和slc22a3基因以及父系表达的长非编码RNA(LncRNA)Airn。虽然已知Igf2r和Airn是相互印记的，但在体内印记表达的时间和伴随的表观遗传学变化尚未得到很好的表征。在这里，我们展示了DNA甲基化和组蛋白修饰在Igf2r/Airn基因座上的谱系和时间特异性调节，与原肠形成过程中印迹表达的差异建立相关。我们的结果表明，在E6.5上胚中，Igf2r在两个等位基因中都有表达。在原肠形成开始后，该基因座印记在胚胎谱系中，lncRNA Airn来自父亲的等位基因表达，而Igf2r仅限于母亲的等位基因表达。我们记录了在胚胎外和胚胎组织中差异丰富的等位基因特异性组蛋白修饰。我们还首次记录了在原肠形成过程中DNA甲基化的等位基因特异性传播，同时建立了Igf2r的印迹表达。重要的是，我们表明印记表达在胚外谱系中没有改变，即使母体DMR2甲基化传播确实发生，这表明不同的机制在胚胎和胚外谱系中发挥作用。这些结果表明，与着床前相似，原肠形成代表了体内动态谱系特异性表观遗传调节的窗口。本文的在线版本(doi：10.1186/s13072-0150003-y)包含补充材料，授权用户可以使用。
Appropriate epigenetic regulation of gene expression during lineage allocation and tissue differentiation is required for normal development. One example is genomic imprinting, which is defined as parent-of-origin mono-allelic gene expression. Imprinting is established largely due to epigenetic differences arriving in the zygote from sperm and egg haploid genomes. In the mouse, there are approximately 150 known imprinted genes, many of which occur in imprinted gene clusters that are regulated together. One imprinted cluster includes the maternally expressed Igf2r, Slc22a2, and Slc22a3 genes and the paternally expressed long non-coding RNA (lncRNA) Airn. Although it is known that Igf2r and Airn are reciprocally imprinted, the timing of imprinted expression and accompanying epigenetic changes have not been well characterized in vivo. Here we show lineage- and temporal-specific regulation of DNA methylation and histone modifications at the Igf2r/Airn locus correlating with differential establishment of imprinted expression during gastrulation. Our results show that Igf2r is expressed from both alleles in the E6.5 epiblast. After gastrulation commences, the locus becomes imprinted in the embryonic lineage with the lncRNA Airn expressed from the paternal allele and Igf2r restricted to maternal allele expression. We document differentially enriched allele-specific histone modifications in extraembryonic and embryonic tissues. We also document for the first time allele-specific spreading of DNA methylation during gastrulation concurrent with establishment of imprinted expression of Igf2r. Importantly, we show that imprinted expression does not change in the extraembryonic lineage even though maternal DMR2 methylation spreading does occur, suggesting distinct mechanisms at play in embryonic and extraembryonic lineages. These results indicate that similar to preimplantation, gastrulation represents a window of dynamic lineage-specific epigenetic regulation in vivo. The online version of this article (doi:10.1186/s13072-015-0003-y) contains supplementary material, which is available to authorized users.
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影响因子：
10.5
作者：
Zwart, R;Sleutels, F;Barlow, DP
通讯作者：
Barlow, DP
影响因子：
4.6
作者：
Santoro, Federica;Mayer, Daniela;Pauler, Florian M.
通讯作者：
Pauler, Florian M.
影响因子：
5.3
作者：
Sleutels, F;Barlow, DP
通讯作者：
Barlow, DP
影响因子：
2.6
作者：
Lerchner, W;Barlow, DP
通讯作者：
Barlow, DP
CCCTC 结合因子诱饵蛋白对染色体内环的干扰消除了人胰岛素样生长因子 II 的基因组印记
DOI：
10.1083/jcb.201101021
发表时间：
2011-05-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Zhang H;Niu B;Hu JF;Ge S;Wang H;Li T;Ling J;Steelman BN;Qian G;Hoffman AR
通讯作者：
Hoffman AR