Mlynarczyk-Evans Susanna, Royce-Tolland Morgan, Alexander Mary Kate, Andersen Angela A, Kalantry Sundeep, Gribnau Joost, Panning Barbara
Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, USA.
PLoS Biol. 2006 Jun;4(6):e159. doi: 10.1371/journal.pbio.0040159. Epub 2006 May 9.
Early in the development of female mammals, one of the two X chromosomes is silenced in half of cells and the other X chromosome is silenced in the remaining half. The basis of this apparent randomness is not understood. We show that before X-inactivation, the two X chromosomes appear to exist in distinct states that correspond to their fates as the active and inactive X chromosomes. Xist and Tsix, noncoding RNAs that control X chromosome fates upon X-inactivation, also determine the states of the X chromosomes prior to X-inactivation. In wild-type ES cells, X chromosomes switch between states; among the progeny of a single cell, a given X chromosome exhibits each state with equal frequency. We propose a model in which the concerted switching of homologous X chromosomes between mutually exclusive future active and future inactive states provides the basis for the apparently random silencing of one X chromosome in female cells.
在雌性哺乳动物发育早期，两条X染色体中的一条在一半细胞中失活，另一条在其余一半细胞中失活。这种明显随机性的基础尚不清楚。我们发现，在X染色体失活之前，两条X染色体似乎处于不同状态，这与它们作为活性X染色体和失活X染色体的命运相对应。Xist和Tsix是在X染色体失活时控制其命运的非编码RNA，它们也决定了X染色体在失活前的状态。在野生型胚胎干细胞中，X染色体在不同状态间转换；在单个细胞的后代中，给定的一条X染色体以相同频率呈现每种状态。我们提出了一个模型，其中同源X染色体在相互排斥的未来活性状态和未来失活状态之间的协同转换，为雌性细胞中一条X染色体的明显随机失活提供了基础。
