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生殖系印记。

Imprinting in the germ line.

作者信息

Mann J R

机构信息

Section of Mammalian Development, Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010-3011, USA.

出版信息

Stem Cells. 2001;19(4):287-94. doi: 10.1634/stemcells.19-4-287.

Abstract

Genomic imprinting is an epigenetic system of gene regulation in mammals. It determines the parent-of-origin-dependent expression of a small number of imprinted genes during development, i.e., the maternal allele is inactive while the paternal is active, or vice versa. Imprinting is imparted in the germ line and involves differential DNA methylation such that particular DNA regions become methylated in one sex of germ line but not in the other. Inheritance of these differential egg and sperm methylation states is then transmitted to somatic cells, where they lead to differential maternal and paternal allelic activity, or monoallelic expression. Increasing evidence indicates that the inherited and stable differential allelic methylation regulates monoallelic expression by influencing the activity of gene regulatory elements-for one allele the element is switched off by methylation, while for the other the element is left potentially active by the lack of methylation. An interesting feature of the germ line is that, despite the presence of genomic imprinting, either as imprints inherited from the zygote or as new imprints imparted according to germ cell sex, imprinted genes are biallelically expressed as if imprints were not present. One explanation for this observation is that imprints have no influence over the germ cell's transcriptional machinery, i.e., imprinting may be neutralized in the germ cell lineage. This phenomenon may have a common basis with other unique features of the germ line, such as totipotency, perhaps in some unique aspect of chromatin structure.

摘要

基因组印记是哺乳动物中一种基因调控的表观遗传系统。它决定了少数印记基因在发育过程中依赖亲本来源的表达,即母本等位基因不活跃而父本等位基因活跃,反之亦然。印记在生殖系中形成,涉及DNA甲基化差异,使得特定的DNA区域在一种性别的生殖系中发生甲基化,而在另一种性别的生殖系中则不发生甲基化。这些卵子和精子甲基化差异状态的遗传随后传递给体细胞,在体细胞中它们导致母本和父本等位基因的差异活性,即单等位基因表达。越来越多的证据表明,遗传的和稳定的等位基因甲基化差异通过影响基因调控元件的活性来调节单等位基因表达——对于一个等位基因,该元件因甲基化而关闭,而对于另一个等位基因,该元件因缺乏甲基化而可能保持活性。生殖系的一个有趣特征是,尽管存在基因组印记,无论是作为从合子继承的印记还是根据生殖细胞性别赋予的新印记,印记基因都是双等位基因表达,就好像不存在印记一样。对这一观察结果的一种解释是,印记对生殖细胞的转录机制没有影响,即印记可能在生殖细胞谱系中被中和。这种现象可能与生殖系的其他独特特征,如全能性,在染色质结构的某些独特方面有共同的基础。

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