Imprinting errors and developmental asymmetry
Imprinting errors and developmental asymmetry
复制标题
DOI：
10.1098/rstb.2003.1323
复制
发表时间：
2003-08-29
期刊：
影响因子：
--
通讯作者：
Bestor, TH
中科院分区：
文献类型：
--
作者：
Bestor, TH
在最广泛的意义上，有两种机制可以使脊椎动物的基因表达消失。第一种是基于积极和消极调节因子的集体作用效应，被称为激活和抑制；第二种是独立于积极调节因素，但基于受影响基因的历史，被称为沉默。再次从最广泛的意义上说，印迹基因、X失活基因、转座子启动子受到沉默，而非表达组织中组织特异性基因的启动子受到激活和抑制的控制。印迹基因通过未知的机制从沉默中逃脱，可能导致发育异常，并容易导致胚胎畸形的形成。由11p15.5染色体上基因印记缺失引起的一种发育障碍是贝克威思-魏德曼综合征（BWS）。长期以来，人们一直认为这种综合征在同卵双胞胎中很常见；双胞胎几乎总是不一致的BWS，几乎所有的双胞胎都是女性。一种基于DNA甲基转移酶DNMT1核质运输的随机误差的印迹丢失模型，或者一种父亲表达的功能，反对母亲抑制的生长增强基因的维持甲基化，被提出来解释同卵双胞胎中BWS的复杂遗传学。
There are, in the broadest sense, two mechanisms by which gene expression can be extinguished in vertebrates. The first of these is based on mass action effects of positive and negative regulatory factors and is termed activation and repression; the second is independent of positive regulatory factors but is based on the history of the affected gene and is termed silencing. It can be said, again in the broadest sense, that imprinted genes, genes subject to X inactivation, and transposon promoters are subject to silencing, while the promoters of tissue-specific genes in non-expressing tissues are controlled by activation and repression. The escape of imprinted genes from silencing through unknown mechanisms can cause developmental abnormalities and can predispose to the formation of embryonal turnouts. One developmental disorder caused by loss of imprinting of genes on chromosome 11p15.5 is Beckwith-Wiedemann syndrome (BWS). This syndrome has long been known to be inexplicably common in monozygotic twins; the twins are nearly always discordant for BWS, and nearly all twins are female. A loss of imprinting model based on stochastic errors in the nucleocytoplasmic trafficking of the DNA methyltransferase DNMT1, or a paternally expressed function that opposes maintenance methylation of maternally repressed growth-enhancing genes, is proposed to explain the perplexing genetics of BWS in monozygotic twins.