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一个胚胎学故事:分析控制小鼠胚胎干细胞中 Xist 表达的基因调控网络。

An embryonic story: analysis of the gene regulative network controlling Xist expression in mouse embryonic stem cells.

机构信息

Institut Pasteur, Unité de Génétique Moléculaire Murine, CNRS URA2578, Paris, France.

出版信息

Bioessays. 2010 Jul;32(7):581-8. doi: 10.1002/bies.201000019.

Abstract

In mice, dosage compensation of X-linked gene expression is achieved through the inactivation of one of the two X-chromosomes in XX female cells. The complex epigenetic process leading to X-inactivation is largely controlled by Xist and Tsix, two non-coding genes of opposing function. Xist RNA triggers X-inactivation by coating the inactive X, while Tsix is critical for the designation of the active X-chromosome through cis-repression of Xist RNA accumulation. Recently, a plethora of trans-acting factors and cis-regulating elements have been suggested to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X-linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells.

摘要

在小鼠中,通过 XX 雌性细胞中两条 X 染色体之一的失活来实现 X 连锁基因表达的剂量补偿。导致 X 失活的复杂表观遗传过程主要受 Xist 和 Tsix 的控制,这两个非编码基因具有相反的功能。Xist RNA 通过覆盖失活的 X 来触发 X 失活,而 Tsix 通过 cis 抑制 Xist RNA 积累来指定活性 X 染色体,这对 Tsix 至关重要。最近,大量的反式作用因子和顺式调节元件被认为是 Xist、Tsix 或两者的关键调节因子;这些因子包括普遍存在的因子,如 Yy1 和 Ctcf,发育蛋白,如 Nanog、Oct4 和 Sox2,以及 X 连锁调节因子,如 Rnf12。在本文中,我们总结了我们最近在胚胎干细胞(ES)和分化的 ES 细胞中对 Xist 和 Tsix 调控的认识进展。

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