Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes
Allele-specific histone lysine methylation marks regulatory regions at imprinted mouse genes
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DOI：
10.1093/emboj/cdf655
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发表时间：
2002-12-02
期刊：
影响因子：
11.4
通讯作者：
Feil, R
中科院分区：
文献类型：
--
作者：
Fournier, C;Goto, YJ;Feil, R
在不同的真核模型系统中，染色质和基因表达是通过组蛋白尾部的翻译后修饰来调节的。在这项体内研究中，研究了小鼠基因Snrpn、Igf2r和U2af1-rs1的组蛋白甲基化和乙酰化。这些印迹基因都有一个富含cpg的调控元件，甲基化存在于母体等位基因上，起源于雌性生殖系。在这些“差异甲基化区域”（DMRs）上，父本等位基因上的组蛋白H3发生赖氨酸-4甲基化和乙酰化。相反，在母系遗传的等位基因上，染色质被标记为H3赖氨酸-9的高甲基化。在印迹位点的其他区域也检测到赖氨酸-4和赖氨酸-9甲基化的等位基因特异性模式。对于U2af1-rs1基因的DMR，我们确定甲基cpg结合结构域（MBD）蛋白MeCP2、MBD1和MBD3与母体等位基因相关。这些数据支持了MBD蛋白相关的组蛋白去乙酰化酶/染色质重塑复合物被招募到具有甲基化DNA和H3- k9甲基化的亲本等位基因上，并且被H3赖氨酸-4甲基化阻止与相反的等位基因结合。
In different eukaryotic model systems, chromatin and gene expression are modulated by post-translational modification of histone tails. In this in vivo study, histone methylation and acetylation are investigated along the imprinted mouse genes Snrpn, Igf2r and U2af1-rs1. These imprinted genes all have a CpG-rich regulatory element at which methylation is present on the maternal allele, and originates from the female germ line. At these 'differentially methylated regions' (DMRs), histone H3 on the paternal allele has lysine-4 methylation and is acetylated. On the maternally inherited allele, in contrast, chromatin is marked by hypermethylation on lysine-9 of H3. Allele-specific patterns of lysine-4 and lysine-9 methylation are also detected at other regions of the imprinted loci. For the DMR at the U2af1-rs1 gene, we establish that the methyl-CpG-binding-domain (MBD) proteins MeCP2, MBD1 and MBD3 are associated with the maternal allele. These data support the hypothesis that MBD protein-associated histone deacetylase/chromatin-remodelling complexes are recruited to the parental allele that has methylated DNA and H3-K9 methylation, and are prevented from binding to the opposite allele by H3 lysine-4 methylation.