Widespread random monoallelic gene expression (RMAE) effects influence about 10% of human genes. However, the mechanisms by which RME of autosomal genes is established and those by which it is maintained both remain open questions. Because the choice of allelic expression is randomly performed cell-by-cell, the RMAE mechanism is not observable in non-clonal cell populations or in whole tissues. Several target genes of MeCP2, the gene involved in Rett syndrome (RTT), have been previously described as subject to RMAE, suggesting that MeCP2 may be involved in the establishment and/or maintenance of RME of autosomal genes. To improve our knowledge on this largely unknown phenomenon, and to study the role of MeCP2 in RMAE, we compared RMA gene expression profiles in clonal cell cultures expressing wild-type MeCP2 versus mutant MeCP2 from a RTT patient carrying a pathogenic non-sense variant. Our data clearly demonstrated that MeCP2 deficiency does not affect significantly allelic gene expression of X-linked genes, imprinted genes as well as the RMAE profile in the majority of genes. However, the functional deficiency in MeCP2 appeared to disrupt the mono-allelic or the bi-allelic expression of at least 49 genes allowing us to define a specific signature of MECP2 mutated clones.

中文翻译：

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MeCP2参与人类常染色体基因子集的随机单等位基因表达。

广泛的随机单等位基因表达（RMAE）效应影响约10％的人类基因。然而，建立常染色体基因RME的机制以及维持常染色体基因的RME的机制仍然是一个悬而未决的问题。由于等位基因表达的选择是逐个细胞随机进行的，因此在非克隆细胞群体或整个组织中均未观察到RMAE机制。MeCP2的几种靶基因，即涉及Rett综合征（RTT）的基因，先前已被描述为患有RMAE，这表明MeCP2可能参与常染色体RME的建立和/或维持。为了提高我们对这一未知现象的认识，并研究MeCP2在RMAE中的作用，我们在携带病原性无义变体的RTT患者中比较了野生型MeCP2和突变型MeCP2在克隆细胞培养物中的RMA基因表达谱。我们的数据清楚地表明，MeCP2缺乏症不会显着影响X连锁基因，印迹基因以及大多数基因中的RMAE谱等位基因表达。然而，MeCP2的功能缺陷似乎破坏了至少49个基因的单等位基因或双等位基因表达，从而使我们能够定义MECP2突变克隆的特异性标记。