The region 3′ to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene
The region 3′ to Xist mediates X chromosome counting and H3 Lys-4 dimethylation within the Xist gene
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DOI：
10.1038/sj.emboj.7600071
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发表时间：
2004-02-11
期刊：
影响因子：
11.4
通讯作者：
Clerc, P
中科院分区：
文献类型：
--
作者：
Morey, C;Navarro, P;Clerc, P
计数过程感测X染色体/常染色体比率，并确保X染色体失活（XCI）在雌性（XX）而不是雄性（XY）小鼠胚胎中开始。计数由X失活中心调节，该中心包含Xist基因。在XO胚胎干（ES）细胞中缺失Xist的3'端65 kb影响计数并导致分化时不适当的XCI。我们在这里表明，正常的计数可以挽救这些删除的ES细胞使用cre/loxP重新插入，并细化控制计数的元素在一个20 kb的二分域的位置。此外，我们发现，65 kb的缺失也导致不适当的XCI在XY分化的ES细胞，这排除了参与性别特异性机制的启动XCI。在染色质水平上，我们发现Xist基因对应于H3 Lys-4二甲基化的峰，其显著且特异性地受到Xist的缺失30的影响。我们的研究结果提出了可能性，H3赖氨酸-4二甲基化Xist内可能在功能上涉及的计数过程。
A counting process senses the X chromosome/autosome ratio and ensures that X chromosome inactivation (XCI) initiates in the female (XX) but not in the male (XY) mouse embryo. Counting is regulated by the X-inactivation centre, which contains the Xist gene. Deleting 65 kb 3' to Xist in XO embryonic stem (ES) cells affects counting and results in inappropriate XCI upon differentiation. We show here that normal counting can be rescued in these deleted ES cells using cre/loxP re-insertion, and refine the location of elements controlling counting within a 20 kb bipartite domain. Furthermore, we show that the 65 kb deletion also leads to inappropriate XCI in XY differentiated ES cells, which excludes the involvement of sex-specific mechanisms in the initiation of XCI. At the chromatin level, we have found that the Xist gene corresponds to a peak of H3 Lys-4 dimethylation, which is dramatically and specifically affected by the deletion 30 to Xist. Our results raise the possibility that H3 Lys-4 dimethylation within Xist may be functionally implicated in the counting process.