Cohen Dena E, Lee Jeannie T
Howard Hughes Medical Institute, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
Curr Opin Genet Dev. 2002 Apr;12(2):219-24. doi: 10.1016/s0959-437x(02)00289-7.
X-chromosome inactivation leads to divergent fates for two homologous chromosomes. Whether one X remains active or becomes silenced depends on the activity of Xist, a gene expressed only from the inactive X and whose RNA product 'paints' the X in cis. Recent work argues that Xist RNA itself is the acting agent for initiating the silencing step. Xist RNA contains separable domains for RNA localization and chromosome silencing. While no Xist RNA-interacting factors have been identified, a growing collection of chromatin alterations have been identified on the inactive X, including variant histone H2A composition and histone H3 methylation. Some or all of these changes may be critical for chromosome-wide silencing. As none of the silencing proteins identified so far is unique to X chromosome inactivation, the specificity must partly reside in Xist RNA whose spread along the X orchestrates general silencing factors for this specific task.
X染色体失活导致两条同源染色体的命运不同。一条X染色体是保持活跃还是变得沉默取决于Xist的活性，Xist是一个仅从不活跃的X染色体表达的基因，其RNA产物在顺式作用下“标记”该X染色体。最近的研究表明，Xist RNA本身就是启动沉默步骤的作用因子。Xist RNA包含用于RNA定位和染色体沉默的可分离结构域。虽然尚未鉴定出与Xist RNA相互作用的因子，但在不活跃的X染色体上已鉴定出越来越多的染色质改变，包括变体组蛋白H2A组成和组蛋白H3甲基化。其中一些或所有这些变化可能对全染色体沉默至关重要。由于迄今为止鉴定出的沉默蛋白没有一种是X染色体失活所特有的，因此特异性必须部分存在于Xist RNA中，其沿着X染色体的扩散为此特定任务协调一般沉默因子。
