Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene.
Parental imprinting: potentially active chromatin of the repressed maternal allele of the mouse insulin-like growth factor II (Igf2) gene.
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亲代印记：小鼠胰岛素样生长因子 II (Igf2) 基因受抑制的母体等位基因的潜在活性染色质。
DOI：
10.1101/gad.6.10.1843
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发表时间：
1992
影响因子：
10.5
通讯作者：
Surani,MA
中科院分区：
文献类型：
--
作者：
Sasaki,H;Jones,PA;Chaillet,JR;Ferguson-Smith,AC;Barton,SC;Reik,W;Surani,MA
小鼠胰岛素样生长因子II(IGF2)基因位于7号染色体远端(Chr7)，此前已被证明经历了组织特异性的双亲印记。这种印记导致在父系遗传的染色体上表达Igf2，并在发育中的胚胎的大多数组织中抑制母系遗传的等位基因。我们正在使用具有母系复制和远端chr7父系缺陷的胚胎来描述抑制母系等位基因的机制。我们表明，被抑制的Igf2等位基因5‘端的染色质具有潜在的转录活性，而不是异染色质。特别是，由两个强启动子之一组成的CpG岛在两个亲本等位基因上都没有甲基化，强启动子及其周围的DNaseI超敏位点一致地存在于两个亲本染色体上。与染色质状态一致的是，母体Igf2等位基因的初级转录本被检测到低但显著的水平。这些发现不同于在其他情况下观察到的印记，即X染色体失活和小鼠的转基因印记。虽然在DNA甲基化或对这些启动子的核酸酶的敏感性上没有检测到亲本特异性的差异，但我们在第一外显子上游几千碱基的区域观察到了亲本甲基化的差异。亲本Igf2等位基因的不同活性可以通过位于启动子外部的表观遗传修饰或通过在启动子上微妙但尚未确定的修饰来实现。
The mouse insulin-like growth factor II (Igf2) gene, which is located on distal chromosome 7 (Chr7), has been shown previously to undergo tissue-specific parental imprinting. This imprinting results in expression of Igf2 from the paternally inherited chromosome and repression of the maternally inherited allele in most tissues of the developing embryo. We are using embryos with the maternal duplication and paternal deficiency of distal Chr7 to characterize the mechanism that underlies repression of the maternal allele. We show that the chromatin of the 5' region of the repressed Igf2 allele is potentially active for transcription rather than heterochromatic. In particular, a CpG island that comprises one of the two strong promoters is unmethylated at both parental alleles, and DNase I hypersensitive sites in and around the strong promoters are consistently present on both parental chromosomes. In agreement with the chromatin state, primary transcripts from the maternal Igf2 allele have been detected at low but significant levels. These findings differ from observations in other instances of imprinting, namely, X-chromosome inactivation and transgene imprinting in mice. Although no parent-specific differences were detected in either DNA methylation or sensitivity to nucleases at these promoters, we have observed parental methylation differences in a region several kilobases upstream of the first exon. The differential activity of the parental Igf2 alleles could be achieved through epigenetic modifications situated outside the promoters or by subtle and yet unidentified modifications at the promoters.