Plath Kathrin, Mlynarczyk-Evans Susanna, Nusinow Dmitri A, Panning Barbara
Department of Biochemistry & Biophysics, University of California San Francisco, San Francisco, California 94143, USA.
Annu Rev Genet. 2002;36:233-78. doi: 10.1146/annurev.genet.36.042902.092433. Epub 2002 Jun 11.
Dosage compensation in mammals is achieved by the transcriptional inactivation of one X chromosome in female cells. From the time X chromosome inactivation was initially described, it was clear that several mechanisms must be precisely integrated to achieve correct regulation of this complex process. X-inactivation appears to be triggered upon differentiation, suggesting its regulation by developmental cues. Whereas any number of X chromosomes greater than one is silenced, only one X chromosome remains active. Silencing on the inactive X chromosome coincides with the acquisition of a multitude of chromatin modifications, resulting in the formation of extraordinarily stable facultative heterochromatin that is faithfully propagated through subsequent cell divisions. The integration of all these processes requires a region of the X chromosome known as the X-inactivation center, which contains the Xist gene and its cis-regulatory elements. Xist encodes an RNA molecule that plays critical roles in the choice of which X chromosome remains active, and in the initial spread and establishment of silencing on the inactive X chromosome. We are now on the threshold of discovering the factors that regulate and interact with Xist to control X-inactivation, and closer to an understanding of the molecular mechanisms that underlie this complex process.
哺乳动物中的剂量补偿是通过雌性细胞中一条X染色体的转录失活来实现的。从最初描述X染色体失活之时起，就很清楚，必须精确整合多种机制才能实现对这一复杂过程的正确调控。X染色体失活似乎在细胞分化时被触发，这表明它受发育信号的调控。虽然任何数量大于一条的X染色体会被沉默，但只有一条X染色体保持活跃。失活X染色体上的沉默与多种染色质修饰的获得同时发生，导致形成异常稳定的兼性异染色质，这种异染色质在随后的细胞分裂中被忠实地传递下去。所有这些过程的整合需要X染色体上一个称为X染色体失活中心的区域，该区域包含Xist基因及其顺式调控元件。Xist编码一种RNA分子，它在选择哪条X染色体保持活跃以及在失活X染色体上沉默的初始扩散和建立过程中发挥关键作用。我们现在即将发现调控Xist并与之相互作用以控制X染色体失活的因子，并且更接近于理解这一复杂过程背后的分子机制。
