Tinker A V, Brown C J
Department of Medical Genetics, University of British Columbia, 6174 University Boulevard, Vancouver, BC V6T 1Z3, Canada.
Nucleic Acids Res. 1998 Jun 15;26(12):2935-40. doi: 10.1093/nar/26.12.2935.
X chromosome inactivation occurs early in mammalian development to transcriptionally silence one of the pair of X chromosomes in females. The XIST RNA, a large untranslated RNA that is expressed solely from the inactive X chromosome, is implicated in the process of inactivation. As previous studies have shown that the XIST gene is methylated on the active X chromosome, we have treated a mouse/human somatic cell hybrid retaining an active human X chromosome with demethylating agents to determine whether expression of the human XIST gene could be induced. Stable expression of XIST was observed after several rounds of demethylation and stability of XIST expression correlated with the loss of methylation at the three sites analysed. We conclude that methylation is sufficient to inhibit expression of the XIST gene in somatic cell hybrids. No loss of expression was detected for eight other X-linked genes from the active X chromosome that was expressing XIST , suggesting that additional developmental or species-specific factors are required for the inactivation process.
X染色体失活在哺乳动物发育早期发生，使雌性个体中两条X染色体中的一条在转录水平上沉默。XIST RNA是一种仅从失活的X染色体表达的大型非翻译RNA，参与失活过程。由于先前的研究表明XIST基因在活性X染色体上发生甲基化，我们用去甲基化剂处理保留活性人类X染色体的小鼠/人类体细胞杂种，以确定是否可以诱导人类XIST基因的表达。经过几轮去甲基化后观察到XIST的稳定表达，且XIST表达的稳定性与所分析的三个位点甲基化的缺失相关。我们得出结论，甲基化足以抑制体细胞杂种中XIST基因的表达。从表达XIST的活性X染色体上检测到其他八个X连锁基因的表达没有缺失，这表明失活过程需要额外的发育或物种特异性因子。
