7503213742ENSG00000229807ENSMUSG00000086503nan/an/an/an/an/aXist (X-inactive specific transcript) is a non-coding RNA transcribed from the X chromosome of the placental mammals that acts as a major effector of the X-inactivation process.
[7] The Xist RNA, a large (17 kb in humans)[8] transcript, is expressed on the inactive chromosome and not on the active one.
[11] The human Xist gene was discovered by Andrea Ballabio through a cDNA library screening and then characterized in collaboration with Carolyn J.
The process is regulated by several factors, including a region of chromosome X called the X-inactivation center (XIC).
[5] The functional role of the Xist transcript was definitively demonstrated in mouse female ES cells using a novel antisense technology, 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 prevented the formation of Xi and inhibited cis-silencing of X-linked genes.
[14] The X-inactivation process occurs in mice even in the absence of this gene via epigenetic regulation, but Xist is required to stabilize this silencing.
[15] In addition to being expressed in nearly all females, XIST is expressed in narrow developmental contexts in males including human preimplantation embryos, primordial germ cells, testicular germ cell tumors, and a subset of male cancers of diverse lineages.
[8] The Xist RNA gene features a conserved A region, which contains 8 repeats separated by U-rich spacers.
[17] It was initially suggested that repA repeats could fold back on themselves to form local intra-repeat stem-loop structures.
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.
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.
Dicer is an RNAi enzyme and it is believed to cleave the duplex of Xist and Tsix at the beginning of X-inactivation, to small ~30 nucleotide RNAs, which have been termed xiRNAs, These xiRNAs are believed to be involved in repressing Xist on the probable active X chromosome based upon studies.
[citation needed] Pluripotent stem cells express transcription factors Nanog, Oct4 and Sox2 that seem to play a role in repressing Xist.
[30] The PRC2 has been observed to repress Xist expression independent of the Tsix antisense transcript, although the definite mechanism is still not known.
X-inactivation plays a key role in dosage compensation mechanisms that allow for equal expression of the X and autosomal chromosomes.