Histone macroH2A1.2 relocates to the inactive X chromosome after initiation and propagation of X-inactivation.
Histone macroH2A1.2 relocates to the inactive X chromosome after initiation and propagation of X-inactivation.
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DOI：
10.1083/jcb.147.7.1399
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发表时间：
1999-12-27
影响因子：
7.8
通讯作者：
Brockdorff, N
中科院分区：
文献类型：
--
作者：
Mermoud, J E;Costanzi, C;Pehrson, J R;Brockdorff, N
组蛋白macroH2A1.2在成年雌性哺乳动物的失活X染色体（Xi）上积累，因此与X染色体失活有关。我们已经建立了时间macroH2A1.2协会与Xi相对于发病的X-失活分化小鼠胚胎干细胞（ES）使用免疫RNA荧光原位杂交（FISH）。在X失活之前，我们在未分化的XX和XY ES细胞中观察到单个macroH2A1.2致密区域，该区域不与X失活特异性转录物（Xist）RNA共定位，因此似乎不与X染色体相关。这种模式持续到分化的早期阶段，直到第7天。然后含有富含macroH2A1.2结构域的XY细胞的频率下降。相比之下，在XX细胞中，macroH2A1.2显着重新定位到XI。重新定位发生在一个高度同步的波在2-d期间，表明一个精确的调节协会。宏H2A1.2在Xi上积累的时间表明，它对于随机X失活的启动或传播是不必要的。
The histone macroH2A1.2 has been implicated in X chromosome inactivation on the basis of its accumulation on the inactive X chromosome (Xi) of adult female mammals. We have established the timing of macroH2A1.2 association with the Xi relative to the onset of X-inactivation in differentiating murine embryonic stem (ES) cells using immuno-RNA fluorescence in situ hybridization (FISH). Before X-inactivation we observe a single macroH2A1.2-dense region in both undifferentiated XX and XY ES cells that does not colocalize with X inactive specific transcript (Xist) RNA, and thus appears not to associate with the X chromosome(s). This pattern persists through early stages of differentiation, up to day 7. Then the frequency of XY cells containing a macroH2A1.2-rich domain declines. In contrast, in XX cells there is a striking relocalization of macroH2A1.2 to the Xi. Relocalization occurs in a highly synchronized wave over a 2-d period, indicating a precisely regulated association. The timing of macroH2A1.2 accumulation on the Xi suggests it is not necessary for the initiation or propagation of random X-inactivation.