Lessons from imprinted multilocus loss of methylation in human syndromes A step toward understanding the mechanisms underlying these complex diseases
Lessons from imprinted multilocus loss of methylation in human syndromes A step toward understanding the mechanisms underlying these complex diseases
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DOI：
10.4161/epi.5.5.11851
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发表时间：
2010-07-01
期刊：
影响因子：
3.7
通讯作者：
Netchine, Irene
中科院分区：
文献类型：
--
作者：
Azzi, Salah;Rossignol, Sylvie;Netchine, Irene
基因组印记是最重要的表观遗传调控机制之一。在哺乳动物胚胎发育过程中，印记的忠实建立和维持对于个体的正确胚胎发育和出生后发育至关重要。在人类中，许多复杂的综合征（包括罗素银综合征和贝克威斯-威德曼综合征）和癌症与特定基因座的印记缺失（LOI）有关。近年来，越来越多的证据表明，LOI不仅是发生在涉及特定综合征的给定基因座上的孤立事件，而且许多患有给定综合征的患者具有影响两个父母等位基因的多基因座印记缺陷。这一新的证据表明，这些异常发生在受精后胎儿发育期间，并提出了什么机制导致这些多位点印迹缺陷的问题。识别的因素参与的维护和/或建立印迹无疑是至关重要的了解这两个机制的基础印迹调节和中断导致这些复杂的疾病。
Genomic imprinting is one of the most important epigenetic mechanisms of regulation. Faithful establishment and maintenance of imprinting during mammalian fetal development is crucial for correct fetal and postnatal development of the individual. In humans, numerous complex syndromes (including Russell Silver syndrome and Beckwith Wiedemann syndrome) and cancers are associated with loss of imprinting (LOI) at particular loci. Over recent years, there has been increasing evidence that LOI is not only an isolated event occurring at a given locus involved in a particular syndrome, but that many patients with a given syndrome have multilocus imprinting defects affecting both parental alleles. This new evidence demonstrates that these anomalies occur during the post-fertilization period of fetal development and raises the question of what mechanisms lead to these multilocus imprinting defects. Identification of the factors involved in the maintenance and/or the establishment of imprinting is undoubtedly crucial for understanding both the mechanisms underlying imprinting regulation and which disruptions lead to these complex diseases.