Department of Genetics, Carolina Center for Genome Sciences, and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7264, USA.
Development. 2011 May;138(10):2049-57. doi: 10.1242/dev.061176. Epub 2011 Apr 6.
Repression of Xist RNA expression is considered a prerequisite to reversal of X-chromosome inactivation (XCI) in the mouse inner cell mass (ICM), and reactivation of X-linked genes is thought to follow loss of Xist RNA coating and heterochromatic markers of inactivation, such as methylation of histone H3. We analyzed X-chromosome activity in developing ICMs and show that reactivation of gene expression from the inactive-X initiates in the presence of Xist coating and H3K27me3. Furthermore, depletion of Xist RNA coating through forced upregulation of NANOG does not result in altered reactivation kinetics. Taken together, our observations suggest that in the ICM, X-linked gene transcription and Xist coating are uncoupled. These data fundamentally alter our perception of the reactivation process and support the existence of a mechanism to reactivate Xp-linked genes in the ICM that operates independently of loss of Xist RNA and H3K27me3 from the imprinted inactive-X.
抑制 Xist RNA 的表达被认为是小鼠内细胞团（ICM）中逆转 X 染色体失活（XCI）的前提，并且认为 X 连锁基因的重新激活紧随 Xist RNA 覆盖和失活的异染色质标记（如组蛋白 H3 的甲基化）的丢失之后。我们分析了发育中的 ICM 中的 X 染色体活性，并表明从失活 X 上的基因表达的重新激活在 Xist 覆盖和 H3K27me3 的存在下发生。此外，通过强制上调 NANOG 来耗尽 Xist RNA 覆盖并不会导致重新激活动力学发生改变。总之，我们的观察结果表明，在 ICM 中，X 连锁基因转录和 Xist 覆盖是解耦的。这些数据从根本上改变了我们对重新激活过程的认识，并支持存在一种机制，可以在 ICM 中重新激活 Xp 连锁基因，该机制独立于印迹失活 X 上的 Xist RNA 和 H3K27me3 的丢失而发挥作用。
