A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation
A cross-species comparison of escape from X inactivation in Eutheria: implications for evolution of X chromosome inactivation
复制标题
DOI：
10.1007/s00412-011-0343-8
复制
发表时间：
2012-02-01
期刊：
影响因子：
1.6
通讯作者：
Waters, Paul D.
中科院分区：
文献类型：
--
作者：
Al Nadaf, Shafagh;Deakin, Janine E.;Waters, Paul D.
真兽类和有袋类哺乳动物的性染色体剂量补偿是通过 X 染色体失活 (XCI) 转录抑制来实现的，该转录抑制使雌性体细胞中的两条 X 染色体之一沉默。我们最近使用 RNA 荧光原位杂交 (FISH) 来表明，在单个细胞核中，有袋动物 X 失活（在不存在 XIST 的情况下）是逐个基因发生的，并且逃避失活是随机的且与基因位置无关。由于缺乏真兽代表成纤维细胞系的类似数据，因此缺乏有意义的比较。因此，我们使用 RNA-FISH 来检查从三个远亲真兽模型物种获得的成纤维细胞系中的 XCI：非洲草原象 (Loxodonta africana)、小鼠 (Mus musculus) 和人类 (Homo sapiens)。我们发现，与直系同源有袋动物 X 不同，真兽类 X 保守区 (XCR) 的失活通常是完全的。对女性、小鼠和大象间期细胞核进行的双色 RNA-FISH 显示 XCR 位点在几乎所有细胞核中均具有单等位基因表达。然而，我们发现位于进化上独特的最近添加区域 (XAR) 的许多基因座显示出具有一个或两个活性 X 等位基因的可重复的基因座特异性细胞核频率。我们认为有袋动物 XCI 保留了一种古老的不完全沉默机制的特征，该机制通过 XIST 基因的进化而增强，该基因逐渐稳定了真兽类 XCR。相比之下，最近添加的真兽类 X 区域显示出不完整的失活特征，类似于在进化上独特的有袋动物 X 和独立进化的单孔类 X 染色体上观察到的情况。
Sex chromosome dosage compensation in both eutherian and marsupial mammals is achieved by X chromosome inactivation (XCI)-transcriptional repression that silences one of the two X chromosomes in the somatic cells of females. We recently used RNA fluorescent in situ hybridization (FISH) to show, in individual nuclei, that marsupial X inactivation (in the absence of XIST) occurs on a gene-by-gene basis, and that escape from inactivation is stochastic and independent of gene location. In the absence of similar data from fibroblast cell lines of eutherian representatives, a meaningful comparison is lacking. We therefore used RNA-FISH to examine XCI in fibroblast cell lines obtained from three distantly related eutherian model species: African savannah elephant (Loxodonta africana), mouse (Mus musculus) and human (Homo sapiens). We show that, unlike the orthologous marsupial X, inactivation of the X conserved region (XCR) in eutherians generally is complete. Two-colour RNA-FISH on female human, mouse and elephant interphase nuclei showed that XCR loci have monoallelic expression in almost all nuclei. However, we found that many loci located in the evolutionarily distinct recently added region (XAR) displayed reproducible locus-specific frequencies of nuclei with either one or two active X alleles. We propose that marsupial XCI retains features of an ancient incomplete silencing mechanism that was augmented by the evolution of the XIST gene that progressively stabilized the eutherian XCR. In contrast, the recently added region of the eutherian X displays an incomplete inactivation profile similar to that observed on the evolutionarily distinct marsupial X and the independently evolved monotreme X chromosomes.