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X染色体失活的最新进展。

Recent advances in X-chromosome inactivation.

作者信息

Heard Edith

机构信息

CNRS UMR 218, Curie Institute, 26 rue d'Ulm, Paris 75005, France.

出版信息

Curr Opin Cell Biol. 2004 Jun;16(3):247-55. doi: 10.1016/j.ceb.2004.03.005.

Abstract

X inactivation is the silencing one of the two X chromosomes in XX female mammals. Initiation of this process during early development is controlled by the X-inactivation centre, a complex locus that determines how many, and which, X chromosomes will be inactivated. It also produces the Xist transcript, a remarkable RNA that coats the X chromosome in cis and triggers its silencing. Xist RNA coating induces a cascade of chromatin changes on the X chromosome, including the recruitment of Polycomb group proteins. This results in an inactive state that is initially labile, but may be further locked in by epigenetic marks such as DNA methylation. In mice, X inactivation has recently been found to be much more dynamic than previously thought during early pre-implantation development. The paternal X chromosome is initially inactivated in all cells of cleavage-stage embryos and then selectively reactivated in the subset of cells that will form the embryo, with random X inactivation occurring thereafter.

摘要

X染色体失活是雌性XX哺乳动物中两条X染色体之一的沉默过程。早期发育过程中这一过程的启动由X染色体失活中心控制,这是一个复杂的基因座,它决定有多少条以及哪条X染色体会失活。它还产生Xist转录本,这是一种非凡的RNA,它顺式覆盖X染色体并触发其沉默。Xist RNA覆盖诱导X染色体上一系列染色质变化,包括多梳蛋白家族蛋白的募集。这导致一种最初不稳定的失活状态,但可能会被诸如DNA甲基化等表观遗传标记进一步锁定。在小鼠中,最近发现X染色体失活在植入前早期发育过程中比以前认为的要动态得多。父本X染色体在卵裂期胚胎的所有细胞中最初是失活的,然后在将形成胚胎的细胞亚群中被选择性地重新激活,此后发生随机的X染色体失活。

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