Allele-specific H3K79 Di- versus trimethylation distinguishes opposite parental alleles at imprinted regions.

Allele-specific H3K79 Di- versus trimethylation distinguishes opposite parental alleles at imprinted regions.
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等位基因特异性 H3K79 二甲基化与三甲基化可区分印记区域的相反亲本等位基因。

DOI:
10.1128/mcb.01537-09
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发表时间:
2010
影响因子:
5.3
通讯作者:
Szabo,PiroskaE
Szabo,PiroskaE
中科院分区:
生物学2区
文献类型:
--
作者:
Singh,Purnima;Han,Li;Rivas,GuillermoE;Lee,Dong-Hoon;Nicholson,ThomasB;Larson,GarrettP;Chen,Taiping;Szabo,PiroskaE

文献摘要

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印记基因表达对应于亲本等位基因特异性 DNA CpG 甲基化和染色质组成。组蛋白尾部共价修饰已被广泛研究,但尚不清楚组蛋白球状结构域的修饰是否也可以区分亲本等位基因。使用多重染色质免疫沉淀-单核苷酸引物延伸 (ChIP-SNuPE) 测定,我们测量了 H19/Igf2 印迹域上 H3K79 甲基化和 H4K91 乙酰​​化的等位基因特异性富集。 H3K79me1、H3K79me2 和 H4K91ac 在父系表达的 Igf2 基因座上表现出父系特异性富集,而 H3K79me3 在母系表达的 H19 基因座上表现出父系偏向,包括父系甲基化印记控制区 (ICR)。我们发现这些等位基因特异性差异取决于母体 ICR 等位基因中 CTCF 的结合。我们分析了另外 11 个差异甲基化区域 (DMR),发现一般来说,H3K79me3 与 CpG 甲基化等位基因相关,而 H3K79me1、H3K79me2 和 H4K91ac 富集特定于非甲基化等位基因。我们的数据表明,球状组蛋白结构域中的等位基因特异性差异可能构成印记基因上的一层“组蛋白代码”。
Imprinted gene expression corresponds to parental allele-specific DNA CpG methylation and chromatin composition. Histone tail covalent modifications have been extensively studied, but it is not known whether modifications in the histone globular domains can also discriminate between the parental alleles. Using multiplex chromatin immunoprecipitation-single nucleotide primer extension (ChIP-SNuPE) assays, we measured the allele-specific enrichment of H3K79 methylation and H4K91 acetylation along theH19/Igf2imprinted domain. Whereas H3K79me1, H3K79me2, and H4K91ac displayed a paternal-specific enrichment at the paternally expressedIgf2locus, H3K79me3 was paternally biased at the maternally expressedH19locus, including the paternally methylated imprinting control region (ICR). We found that these allele-specific differences depended on CTCF binding in the maternal ICR allele. We analyzed an additional 11 differentially methylated regions (DMRs) and found that, in general, H3K79me3 was associated with the CpG-methylated alleles, whereas H3K79me1, H3K79me2, and H4K91ac enrichment was specific to the unmethylated alleles. Our data suggest that allele-specific differences in the globular histone domains may constitute a layer of the “histone code” at imprinted genes.