Heterochromatinization of the inactive X chromosome and its maintenance mechanism

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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.