The XIST gene is the only gene which is expressed from the inactive but not from the active X chromosome. This unique gene encodes a 17 kb alternatively spliced, processed transcript which is not translated into a protein but which is associated with the inactive X chromosome. The inactivation process apparently involves expression, stabilisation and localisation of the XIST transcript. While most of the several thousand X-linked genes are stably inactivated, the TIMP1 gene is expressed at a high frequency in somatic cell hybrids. We are exploring the nature of this reactivation to establish a hierarchy to the features involved in maintenance of X inactivation.
Mutations affecting X-linked genes cause relatively common and often serious medical disorders.
Insights into the underlying mechanisms of regulation unique to this chromosome is therefore of clinical interest. We are collaborating with Dr. Wendy Robinson's research group at the B.C. Children's Hospital to examine the sources of skewed inactivation in female embryonic and extraembryonic tissues. We are also examining the role of X-linked gene expression in the development of neoplasia. C.J. The role of the X chromosome in cancer. Brown, C.J. and Baldry, S.E.L. Evidence that heteronuclear proteins interact with the XIST RNA in vitro.