Methylation at mouse Cdkn1c is acquired during postimplantation development and functions to maintain imprinted expression

Methylation at mouse Cdkn1c is acquired during postimplantation development and functions to maintain imprinted expression
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DOI:
10.1016/j.ygeno.2004.08.004
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发表时间:
2004-12-01
期刊:
影响因子:
4.4
通讯作者:
Davis, TL
Davis, TL
中科院分区:
生物学3区
文献类型:
--
作者:
Bhogal, B;Arnaudo, A;Davis, TL

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印记基因的单等位基因表达通常与差异甲基化相关。甲基化可以作为配子印记标记遗传,也可以在受精后获得。在这里,我们的特点与小鼠Cdkn1c基因的差异甲基化区域,并发现它是局限于一个CpG岛,开始600 bp 5'的启动子,并延伸到转录单位。我们的分析表明,该区域的甲基化不是从精子中遗传的,而是在植入后在父系等位基因上特异性获得的,并且依赖于KvDMR 1。我们进一步证明,虽然甲基化是需要保持沉默的父亲Cdkn1c等位基因,它不是一个先决条件,在这个位点上建立单等位基因表达。在差异甲基化发生之前,额外的表观遗传修饰必须在区分Cdkn1c的亲本等位基因并影响其表达方面发挥作用。(C)2004年爱思唯尔公司All rights reserved.
Monoallelic expression of imprinted genes is generally associated with differential methylation. Methylation may be inherited as the gametic imprinting mark or may be acquired postfertilization. Here, we characterize a differentially methylated region associated with the mouse Cdkn1c gene and find that it is confined to a CpG island that begins 600 bp 5' of the promoter and extends into the transcription unit. Our analysis indicates that methylation of this region is not inherited from sperm, is acquired specifically on the paternal allele following implantation, and is dependent on KvDMR1. We further demonstrate that although methylation is required for maintaining silencing of the paternal Cdkn1c allele, it is not a prerequisite for the establishment of monoallelic expression at this locus. Prior to the onset of differential methylation, additional epigenetic modifications must play a role in distinguishing the parental alleles of Cdkn1c and influencing their expression. (C) 2004 Elsevier Inc. All rights reserved.