THE HUMAN X-INACTIVATION CENTER IS NOT REQUIRED FOR MAINTENANCE OF X-CHROMOSOME INACTIVATION

X-CHROMOSOME inactivation occurs early in mammalian female development to achieve dosage compensation with males(1). Although it is widely accepted that this inactivation requires the presence in cis of the X-inactivation centre (XIC)(2-5), it is not known whether the XIC is required for the initiation, promulgation or maintenance of X inactivation(6,7). The XIST gene, which is localized within the XIC interval on both the human and mouse X chromosomes, is constitutively expressed from inactive X chromosomes(8-10), suggesting a possible role in the maintenance of X inactivation. To address whether the presence of the XIC, including the XIST gene, is continuously required for the maintenance of X-chromosome inactivation, we have analysed the transcriptional activity of a number of X-linked genes in mouse/human somatic cell hybrids retaining an intact human inactive X chromosome or derivatives of the inactive X chromosome lacking the XIC. Genes subject to X inactivation remain transcriptionally silent despite the loss of the XIC, demonstrating that the presence of the XIC is not required for the maintenance of X inactivation in somatic cells.