Nora Elphège P, Heard Edith
Epigenese et developpement des mammiferes, Institut Curie, Paris, France.
Biol Aujourdhui. 2010;204(3):199-204. doi: 10.1051/jbio/2010013. Epub 2010 Oct 13.
Early development of female mammals is accompanied by transcriptional inactivation of one of their two X chromosomes. This process, known as X-chromosome inactivation, relies on monoallelic activation of the Xist gene. Xist produces a non-coding RNA that can coat the chromosome from which it is transcribed in cis and trigger its silencing. How Xist expression is controlled and how it initiates transcriptional repression are central questions for our understanding of how this chromosome-wide monoallelic program is expressed. Several trans-acting factors have been identified as regulators of Xist expression. Interestingly, some Xist activators are encoded by the X chromosome itself, thereby efficiently promoting Xist expression in females (XX) but not in males (XY). Female cells also display transient physical pairing between their two X chromosomes at the level of their Xics (X inactivation centers) during the time window when X inactivation is initiated. It has been proposed that these pairing events may play a role in Xist activation and its monoallelic regulation. Xist RNA accumulates over the X chromosome from which it is expressed and rapidly triggers the exclusion of the transcription machinery. Genic sequences are initially located outside of this Xist RNA coated domain but as they become progressively silenced they are relocated into this silent nuclear compartment created by Xist. However genes are not all silenced with the same kinetics. Furthermore, some genes can escape X inactivation and remain located outside the Xist-coated compartment. Recent findings have revealed that young, active LINE-1 retrotransposons are expressed from the inactive X chromosome and may facilitate X inactivation, particularly in regions of the X that would otherwise be prone to escape.
雌性哺乳动物的早期发育伴随着两条X染色体之一的转录失活。这个过程，即X染色体失活，依赖于Xist基因的单等位基因激活。Xist产生一种非编码RNA，它可以顺式覆盖其转录所在的染色体并触发其沉默。Xist的表达是如何被控制的，以及它如何启动转录抑制，是我们理解这个全染色体范围的单等位基因程序如何表达的核心问题。几种反式作用因子已被确定为Xist表达的调节因子。有趣的是，一些Xist激活因子由X染色体本身编码，从而有效地促进雌性（XX）而非雄性（XY）中的Xist表达。在启动X失活的时间窗口内，雌性细胞在其Xic（X失活中心）水平上还表现出两条X染色体之间的短暂物理配对。有人提出，这些配对事件可能在Xist激活及其单等位基因调控中起作用。Xist RNA在其表达所在的X染色体上积累，并迅速触发转录机制的排除。基因序列最初位于这个被Xist RNA覆盖的区域之外，但随着它们逐渐沉默，它们被重新定位到由Xist创建的这个沉默的核区室中。然而，基因并非都以相同的动力学被沉默。此外，一些基因可以逃避X失活并仍位于被Xist覆盖的区室之外。最近的研究发现，年轻的、活跃的LINE-1逆转录转座子从失活的X染色体表达，并且可能促进X失活，特别是在X染色体上原本容易逃避失活的区域。
