Regulation of X-chromosome inactivation by the X-inactivation centre

X-chromosome inactivation (XCI) is controlled by a complex locus termed the X-inactivation centre (Xic).Chromosome-wide silencing is triggered through expression of Xist, a long non-coding RNA (ncRNA) that is upregulated on one of the two X chromosomes in differentiating XX cells.XCI can be imprinted or random, and both forms require Xist but have different Xic requirements.During random XCI, the Xist promoter is repressed, directly or indirectly, by a combination of factors including pluripotency factors, which ensure that Xist is only expressed in differentiated cells.Several X-linked elements/factors ensure that Xist is upregulated only in cells with more than one X chromosome.Monoallelic Xist expression may be regulated by several mechanisms, including: imprinting (maternal repression); low probability of Xist activation followed by an Xist-mediated negative feedback loop; secondary selection against aberrant XCI patterns; asymmetry introduced when physical interactions between the Tsix alleles occur; and the existence of posed asymmetric and switchable fates between the two X chromosomes before XCI.The X/autosome (X/A) ratio influences the number of X chromosomes that will remain active during random XCI, so that diploid cells only keep one active X chromosome and tetraploid cells tend to keep two active X chromosomes, irrespective to their total X chromosome number.The inactive state of the X chromosome can be reversed in specific tissues and at specific stages of development, as well as during cloning or induced pluripotency experiments in mice.Different mammals may exploit different mechanisms of Xist regulation during early embryogenesis.