Heterochromatinization of the inactive X chromosome and its maintenance mechanism

在哺乳动物雌性体细胞中，两条X染色体中的一条失活并形成异染色质。一旦建立，失活的X染色体（Xi）在整个体细胞分裂过程中稳定维持，然而如果将Xi引入未分化的细胞中，它会失去异染色质特性并容易再活化。某些胚胎癌（EC）细胞系保留Xi，而不管其未分化状态。我们以前已经证明，Xi在MC 12 EC细胞系中，不像在体细胞中，是不稳定的，自发地重新激活。为了寻找导致Xi在MC 12 EC细胞中不稳定的基因，我们筛选了一系列仅在未分化细胞中表达的基因。这些基因中的一个在MC12 EC细胞的一小部分中表达，然而，MC12中该基因的异位表达增加了失活X染色体的染色体范围再活化的频率。因此，该基因可使MC 12 EC细胞中的Xi的兼性异染色质不稳定。

In mammalian female somatic cells, one of the two X chromosomes is inactivated and forms heterochromatin. Once established, the inactive X chromosome (Xi) is stably maintained throughout somatic cell divisions, however if Xi introduced into undifferentiated cells, it looses heterochromatic properties and readily reactivated. Certain embryonal carcinoma (EC) cell lines retain Xi, irrespective of its undifferentiated state. We have previously demonstrated that Xi in the MC12 EC cell line is, unlike that in somatic cells, is unstable and reactivated spontaneously. To search genes responsible to this instability of Xi in MC12 EC cells, we screened a series of genes that are expressed exclusively from undifferentiated cells. One of these genes was expressed in a small fraction of the MC12 EC cells, however, ectopic expression of the gene in MC12 increases the frequencies of chromosome-wide reactivation of the inactive X chromosome. Thus, this gene may destabilize facultative heterochromatin of Xi in MC12 EC cells.