germ cell tumors, and a subset of male cancers of diverse lineages. It may be involved in the dosage compensation of supernumerary X chromosomes in the latter two cases. Gene location The human Xist RNA gene is located on the long (q) arm of the X chromosome. The Xist RNA gene consists of conserved repeats within its structure and is also largely localized in the nucleus. The Xist RNA gene consists of an A region, which contains 8 repeats separated by U-rich spacers. The A region appears to contain two long stem-loop structures that each include four repeats. An ortholog of the Xist RNA gene in humans has been identified in mice. This ortholog is a 15 kb Xist RNA gene that is also localized in the nucleus. However, the ortholog does not consist of conserved repeats. The gene also consists of an Xist Inactivation Center (XIC), which plays a major role in X-inactivation. Transcript organization A region The Xist RNA contains a region of conservation called the repeat A (repA) region that contains up to nine repeated elements. It was initially suggested that repA repeats could fold back on themselves to form local intra-repeat stem-loop structures. Later work using in vitro biochemical structure probing proposed several inter-repeat stem-loop structures. A recent study using in vivo biochemical probing and comparative sequence analysis proposed a revision of the repA structure model that includes both intra-repeat and inter-repeat folding found in previous models as well as novel features (see Figure). In addition to its agreement with the in vivo data, this revised model is highly conserved in rodents and mammals (including humans) suggesting functional importance for repA structure. Although the exact function of the repA region is uncertain, it was shown that the entire region is needed for efficient binding to the Suz12 protein. C region The Xist RNA directly binds to the inactive X-chromosome through a chromatin binding region of the RNA transcript. The Xist chromatin binding region was first elucidated in female mouse fibroblastic cells. The primary chromatin binding region was shown to localize to the C-repeat region. The chromatin-binding region was functionally mapped and evaluated by using an approach for studying noncoding RNA function in living cells called peptide nucleic acid (PNA) interference mapping. In the reported experiments, a single 19-bp antisense cell-permeating PNA targeted against a particular region of Xist RNA caused the disruption of the Xi. The