Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes.
Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes.
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DOI：
10.1093/nar/gkq1230
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发表时间：
2011-06
影响因子：
14.9
通讯作者：
Oakey RJ
中科院分区：
文献类型：
--
作者：
Monk D;Arnaud P;Frost JM;Wood AJ;Cowley M;Martin-Trujillo A;Guillaumet-Adkins A;Iglesias Platas I;Camprubi C;Bourc'his D;Feil R;Moore GE;Oakey RJ
印迹反转录转座基因具有共同的基因组组织，包括启动子相关的差异甲基化区（DMR）和多外显子“宿主”基因的内含子内的位置。在小鼠中，至少有一种宿主基因的转录本也受到基因组印记的影响。人类逆转录同源物是印迹的，我们发现人类宿主基因没有印迹。这与灵长类进化过程中发生的基因组重排相吻合，这增加了逆转录DMRs与宿主基因之间的分离。为了解决控制印迹逆转录基因表达的机制，我们在DMRs上检测了组蛋白修饰。对于小鼠的逆转录基因，活性标记H3K4me2与未甲基化的父系等位基因相关，而甲基化的母系等位基因在抑制标记中富集，包括H3K9me3和H4K20me3。两个人类逆转录基因显示了活性单等位基因的富集，而不是抑制标记，这表明DNA甲基化和抑制性组蛋白甲基化之间的关系部分解耦，可能是由于这些DMRs的尺寸较小，CpG密度较低。最后，我们发现小鼠和人类宿主基因两侧的基因在一系列组织中是双等位表达的，这表明这些基因座不同于大的印迹簇。
Imprinted retrotransposed genes share a common genomic organization including a promoter-associated differentially methylated region (DMR) and a position within the intron of a multi-exonic ‘host’ gene. In the mouse, at least one transcript of the host gene is also subject to genomic imprinting. Human retrogene orthologues are imprinted and we reveal that human host genes are not imprinted. This coincides with genomic rearrangements that occurred during primate evolution, which increase the separation between the retrogene DMRs and the host genes. To address the mechanisms governing imprinted retrogene expression, histone modifications were assayed at the DMRs. For the mouse retrogenes, the active mark H3K4me2 was associated with the unmethylated paternal allele, while the methylated maternal allele was enriched in repressive marks including H3K9me3 and H4K20me3. Two human retrogenes showed monoallelic enrichment of active, but not of repressive marks suggesting a partial uncoupling of the relationship between DNA methylation and repressive histone methylation, possibly due to the smaller size and lower CpG density of these DMRs. Finally, we show that the genes immediately flanking the host genes in mouse and human are biallelically expressed in a range of tissues, suggesting that these loci are distinct from large imprinted clusters.
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影响因子：
30.8
作者：
Kerkel, Kristi;Spadola, Alexandra;Tycko, Benjamin
通讯作者：
Tycko, Benjamin
影响因子：
5.3
作者：
Brideau, Chelsea M.;Eilertson, Kirsten E.;Soloway, Paul D.
通讯作者：
Soloway, Paul D.
影响因子：
7
作者：
Smith, RJ;Dean, W;Kelsey, G
通讯作者：
Kelsey, G
影响因子：
4.5
作者：
Wood AJ;Roberts RG;Monk D;Moore GE;Schulz R;Oakey RJ
通讯作者：
Oakey RJ
影响因子：
4.5
作者：
Kanber D;Berulava T;Ammerpohl O;Mitter D;Richter J;Siebert R;Horsthemke B;Lohmann D;Buiting K
通讯作者：
Buiting K