A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation
A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation
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DOI：
10.1016/s1097-2765(00)80248-8
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发表时间：
2000-04-01
期刊：
影响因子：
16
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Wutz, A;Jaenisch, R
X失活需要Xist。为了研究X失活的起始，我们构建了全长小鼠Xist cDNA转基因和诱导表达系统，促进了在ES细胞和分化培养物中的可控Xist表达。在胚胎干细胞中，转基因Xist RNA是稳定的，并在顺式中引起长时间的转录抑制。抑制是可逆的，依赖于胚胎干细胞和早期胚胎干细胞分化中持续的Xist表达。分化72小时，失活变为不可逆的，不依赖于Xist。在分化时，常染色体转基因不影响计数，但转基因Xist RNA诱导后期复制和组蛋白H4低乙酰化。Xist必须在分化后48小时内被激活才能实现沉默，这表明Xist的可逆抑制是一个必要的起始步骤，可能发生在雌性细胞正常的X失活过程中。
Xist is required for X inactivation. To study the initiation of X inactivation, we have generated a full-length mouse Xist cDNA transgene and an inducible expression system facilitating controlled Xist expression in ES cells and differentiated cultures. In ES cells, transgenic Xist RNA was stable and caused long-range transcriptional repression in cis. Repression was reversible and dependent on continued Xist expression in ES cells and early ES cell differentiation. By 72 hr of differentiation, inactivation became irreversible and independent of Xist. Upon differentiation, autosomal transgenes did not effect counting, but transgenic Xist RNA induced late replication and histone H4 hypoacetylation. Xist had to be activated within 48 hr of differentiation to effect silencing, suggesting that reversible repression by Xist is a required initiation step that might occur during normal X inactivation in female cells.