X inactivation counting and choice is a stochastic process: Evidence for involvement of an X-linked activator
X inactivation counting and choice is a stochastic process: Evidence for involvement of an X-linked activator
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DOI：
10.1016/j.cell.2007.12.036
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发表时间：
2008-02-08
期刊：
影响因子：
64.5
通讯作者：
Gribnau, Joost
中科院分区：
文献类型：
--
作者：
Monkhorst, Kim;Jonkers, Iris;Gribnau, Joost
雌性哺乳动物细胞通过X染色体失活（XCI）实现X编码基因的剂量补偿。这个过程被认为涉及X染色体计数和选择。为了探索这一过程是如何启动的，我们分析了四倍体的XCI，XXXY和XXYY胚胎干细胞，发现单个细胞核内的每个X染色体都有独立的启动XCI的概率。这一发现表明，一个随机机制指导XCI计数和选择。该概率与X染色体：倍性比成正比，表明存在XCI的X编码激活剂，其本身被XCI过程灭活。删除包括Xist、Tsix和Xite的区域仍然导致雌性细胞中剩余的野生型X染色体上的XCI。这一结果支持了一个随机模型，其中每个X染色体在一个核启动XCI独立和位置的X编码的反式作用XCI激活剂的缺失区域外。
Female mammalian cells achieve dosage compensation of X-encoded genes by X chromosome inactivation (XCI). This process is thought to involve X chromosome counting and choice. To explore how this process is initiated, we analyzed XCI in tetraploid XXXX, XXXY, and XXYY embryonic stem cells and found that every X chromosome within a single nucleus has an independent probability to initiate XCI. This finding suggests a stochastic mechanism directing XCI counting and choice. The probability is directly proportional to the X chromosome:ploidy ratio, indicating the presence of an X-encoded activator of XCI, that itself is inactivated by the XCI process. Deletion of a region including Xist, Tsix, and Xite still results in XCI on the remaining wild-type X chromosome in female cells. This result supports a stochastic model in which each X chromosome in a nucleus initiates XCI independently and positions an X-encoded trans-acting XCI-activator outside the deleted region.