Monfort Asun, Wutz Anton
Institute of Molecular Health Sciences, Swiss Federal Institute of Technology, Hönggerberg, HPL E12, Otto-Stern-Weg 7, Zurich, Switzerland.
F1000Res. 2020 Jan 28;9. doi: 10.12688/f1000research.21362.1. eCollection 2020.
Female mammals express the long noncoding X inactivation-specific transcript ( ) RNA to initiate X chromosome inactivation (XCI) that eventually results in the formation of the Barr body. encompasses half a dozen repeated sequence stretches containing motifs for RNA-binding proteins that recruit effector complexes with functions for silencing genes and establishing a repressive chromatin configuration. Functional characterization of these effector proteins unveils the cooperation of a number of pathways to repress genes on the inactive X chromosome. Mechanistic insights can be extended to other noncoding RNAs with similar structure and open avenues for the design of new therapies to switch off gene expression. Here we review recent advances in the understanding of and on this basis try to synthesize a model for the initiation of XCI.
雌性哺乳动物表达长链非编码X染色体失活特异性转录本( )RNA,以启动X染色体失活(XCI),最终导致巴氏小体的形成。 包含六个重复序列片段,其中含有RNA结合蛋白的基序,这些蛋白招募具有沉默基因功能并建立抑制性染色质构型的效应复合物。对这些效应蛋白的功能表征揭示了多种途径协同作用以抑制失活X染色体上的基因。其机制见解可扩展到具有类似结构的其他非编码RNA,并为设计关闭基因表达的新疗法开辟了途径。在此,我们综述了对 的理解方面的最新进展,并在此基础上尝试构建一个XCI起始的模型。