Epigenetic profiling at mouse imprinted gene clusters reveals novel epigenetic and genetic features at differentially methylated regions
Epigenetic profiling at mouse imprinted gene clusters reveals novel epigenetic and genetic features at differentially methylated regions
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DOI：
10.1101/gr.089185.108
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发表时间：
2009-08-01
期刊：
影响因子：
7
通讯作者：
Beaudet, Arthur L.
中科院分区：
文献类型：
--
作者：
Dindot, Scott V.;Person, Richard;Beaudet, Arthur L.
基因组印记源自等位基因特异性表观遗传修饰，这些修饰在配子发生过程中建立并在整个体细胞发育过程中维持。这些亲本特异性修饰包括 DNA 甲基化和组蛋白翻译后修饰，从而在印记区域产生等位基因特异性活性和抑制域。通过使用高密度基因组平铺阵列，我们从精子、心脏和小脑的 DNA 和染色质免疫沉淀中生成了小鼠 11 个印记基因簇的 DNA 和组蛋白甲基化图谱。我们的分析表明，尽管这些区域内的非 CpG 岛存在高水平的差异 DNA 甲基化，但印记控制区 (ICR) 和次级差异甲基化区域 (DMR) 是通过体细胞组织中 H3K4 三甲基化（活性染色质）和 H3K9 三甲基化（抑制染色质）修饰的重叠模式以及精子差异甲基化区域（sDMR；精子 6 体细胞组织）来识别的。使用这些特征作为 DMR 的共同特征，我们确定了 11 个独特区域，这些区域映射到已知印记基因、未表征基因以及已知印记基因侧翼的基因间区域。这些区域的一个共同特征是存在 CpG 岛和一系列串联重复序列。总的来说，这项研究对印记基因簇上的 DNA 甲基化和组蛋白 H3K4me3 和 H3K9me3 修饰进行了全面分析，并确定了调节基因组印记区域的常见表观遗传和遗传特征。
Genomic imprinting arises from allele-specific epigenetic modifications that are established during gametogenesis and that are maintained throughout somatic development. These parental-specific modifications include DNA methylation and post-translational modifications to histones, which create allele-specific active and repressive domains at imprinted regions. Through the use of a high-density genomic tiling array, we generated DNA and histone methylation profiles at 11 imprinted gene clusters in the mouse from DNA and from chromatin immunoprecipitated from sperm, heart, and cerebellum. Our analysis revealed that despite high levels of differential DNA methylation at non-CpG islands within these regions, imprinting control regions (ICRs) and secondary differentially methylated regions (DMRs) were identified by an overlapping pattern of H3K4 trimethylation (active chromatin) and H3K9 trimethylation (repressive chromatin) modifications in somatic tissue, and a sperm differentially methylated region (sDMR; sperm 6 somatic tissue). Using these features as a common signature of DMRs, we identified 11 unique regions that mapped to known imprinted genes, to uncharacterized genes, and to intergenic regions flanking known imprinted genes. A common feature among these regions was the presence of a CpG island and an array of tandem repeats. Collectively, this study provides a comprehensive analysis of DNA methylation and histone H3K4me3 and H3K9me3 modifications at imprinted gene clusters, and identifies common epigenetic and genetic features of regions regulating genomic imprinting.