Editing X-inactivation (section)

===Xist and Tsix RNAs===
{{Main|Xist}}
The X-inactive specific transcript ([[Xist]]) gene encodes a large [[NcRNA|non-coding RNA]] that is responsible for mediating the specific silencing of the X chromosome from which it is transcribed.<ref>{{cite journal | vauthors = Hoki Y, Kimura N, Kanbayashi M, Amakawa Y, Ohhata T, Sasaki H, Sado T | title = A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse | journal = Development | volume = 136 | issue = 1 | pages = 139–46 | date = January 2009 | pmid = 19036803 | doi = 10.1242/dev.026427 | doi-access = free }}</ref> The inactive X chromosome is coated by Xist RNA,<ref>{{cite journal | vauthors = Ng K, Pullirsch D, Leeb M, Wutz A | title = Xist and the order of silencing | journal = EMBO Reports | volume = 8 | issue = 1 | pages = 34–9 | date = January 2007 | pmid = 17203100 | pmc = 1796754 | doi = 10.1038/sj.embor.7400871 | format = Review Article | quote = [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796754/ Figure 1 Xist RNA encompasses the X from which it is transcribed.] }}</ref> whereas the Xa is not (See Figure to the right). X chromosomes that lack the Xist gene cannot be inactivated.<ref>{{cite journal | vauthors = Penny GD, Kay GF, Sheardown SA, Rastan S, [[Neil Brockdorff|Brockdorff N]] | title = Requirement for Xist in X chromosome inactivation | journal = Nature | volume = 379 | issue = 6561 | pages = 131–7 | year = 1996 | pmid = 8538762 | doi = 10.1038/379131a0 | bibcode = 1996Natur.379..131P | s2cid = 4329368 }}</ref> Artificially placing and expressing the Xist gene on another chromosome leads to silencing of that chromosome.<ref name="Herzing">{{cite journal | vauthors = Herzing LB, Romer JT, Horn JM, Ashworth A | title = Xist has properties of the X-chromosome inactivation centre | journal = Nature | volume = 386 | issue = 6622 | pages = 272–5 | date = March 1997 | pmid = 9069284 | doi = 10.1038/386272a0 | bibcode = 1997Natur.386..272H | s2cid = 4371247 }}</ref><ref name=":6">{{cite journal | vauthors = Lee JT, Jaenisch R | title = Long-range cis effects of ectopic X-inactivation centres on a mouse autosome | journal = Nature | volume = 386 | issue = 6622 | pages = 275–9 | date = March 1997 | pmid = 9069285 | doi = 10.1038/386275a0 | bibcode = 1997Natur.386..275L | s2cid = 10899129 }}</ref>

Prior to inactivation, both X chromosomes weakly express Xist RNA from the Xist gene. During the inactivation process, the future Xa ceases to express Xist, whereas the future Xi dramatically increases Xist RNA production. On the future Xi, the Xist RNA progressively coats the chromosome, spreading out from the XIC;<ref name=Herzing/> the Xist RNA does not localize to the Xa. The [[gene silencing|silencing of genes]] along the Xi occurs soon after coating by Xist RNA.

Like Xist, the [[Tsix]] gene encodes a large RNA which is not believed to encode a protein. The Tsix RNA is transcribed [[antisense]] to Xist, meaning that the Tsix gene overlaps the Xist gene and is [[transcription (genetics)|transcribed]] on the opposite strand of [[DNA]] from the Xist gene.<ref name=":7">{{cite journal | vauthors = Lee JT, Davidow LS, Warshawsky D | title = Tsix, a gene antisense to Xist at the X-inactivation centre | journal = Nature Genetics | volume = 21 | issue = 4 | pages = 400–4 | date = April 1999 | pmid = 10192391 | doi = 10.1038/7734 | s2cid = 30636065 }}</ref> Tsix is a negative regulator of Xist; X chromosomes lacking Tsix expression (and thus having high levels of Xist transcription) are inactivated much more frequently than normal chromosomes.

Like Xist, prior to inactivation, both X chromosomes weakly express Tsix RNA from the Tsix gene. Upon the onset of X-inactivation, the future Xi ceases to express Tsix RNA (and increases Xist expression), whereas Xa continues to express Tsix for several days.

Rep A is a long non coding RNA that works with another long non coding RNA, Xist, for X inactivation. Rep A inhibits the function of Tsix, the antisense of Xist, in conjunction with eliminating expression of Xite. It promotes methylation of the Tsix region by attracting PRC2 and thus inactivating one of the X chromosomes.<ref name=":8">Mercer, T.R., Dinger, M.E., Mattick, J.S., (2009). Long non-coding RNAs: insight into functions. Nature Reviews Genetics. (10) 155–159.</ref>