Editing X-inactivation (section)

====Expressed genes on the inactive X chromosome====
A fraction of the genes along the X chromosome escape inactivation on the Xi. The Xist gene is expressed at high levels on the Xi and is not expressed on the Xa.<ref name="Plath">{{cite journal | vauthors = Plath K, Mlynarczyk-Evans S, Nusinow DA, Panning B | title = Xist RNA and the mechanism of X chromosome inactivation | journal = Annual Review of Genetics | volume = 36 | pages = 233–78 | year = 2002 | pmid = 12429693 | doi = 10.1146/annurev.genet.36.042902.092433 }}</ref> Many other genes escape inactivation; some are expressed equally from the Xa and Xi, and others, while expressed from both chromosomes, are still predominantly expressed from the Xa.<ref name="Carrel L, Willard H 2005 400–404">{{cite journal | vauthors = Carrel L, Willard HF | title = X-inactivation profile reveals extensive variability in X-linked gene expression in females | journal = Nature | volume = 434 | issue = 7031 | pages = 400–4 | date = March 2005 | pmid = 15772666 | doi = 10.1038/nature03479 | bibcode = 2005Natur.434..400C | s2cid = 4358447 }}</ref><ref name="Calabrese JM, Sun W, Song L, Mugford JW, Williams L, Yee D, Starmer J, Mieczkowski P, Crawford GE, Magnuson T 2012 951–63">{{cite journal | vauthors = Calabrese JM, Sun W, Song L, Mugford JW, Williams L, Yee D, Starmer J, Mieczkowski P, Crawford GE, Magnuson T | title = Site-specific silencing of regulatory elements as a mechanism of X inactivation | journal = Cell | volume = 151 | issue = 5 | pages = 951–63 | date = November 2012 | pmid = 23178118 | pmc = 3511858 | doi = 10.1016/j.cell.2012.10.037 }}</ref><ref name="Yang F, Babak T, Shendure J, Disteche CM 2010 614–22">{{cite journal | vauthors = Yang F, Babak T, Shendure J, Disteche CM | title = Global survey of escape from X inactivation by RNA-sequencing in mouse | journal = Genome Research | volume = 20 | issue = 5 | pages = 614–22 | date = May 2010 | pmid = 20363980 | pmc = 2860163 | doi = 10.1101/gr.103200.109 }}</ref> Up to one quarter of genes on the human Xi are capable of escape.<ref name="Carrel L, Willard H 2005 400–404"/> Studies in the mouse suggest that in any given cell type, 3% to 15% of genes escape inactivation, and that escaping gene identity varies between tissues.<ref name="Calabrese JM, Sun W, Song L, Mugford JW, Williams L, Yee D, Starmer J, Mieczkowski P, Crawford GE, Magnuson T 2012 951–63"/><ref name="Yang F, Babak T, Shendure J, Disteche CM 2010 614–22"/>

Many of the genes which escape inactivation are present along regions of the X chromosome which, unlike the majority of the X chromosome, contain genes also present on the [[Y chromosome]]. These regions are termed [[pseudoautosomal]] regions, as individuals of either sex will receive two copies of every gene in these regions (like an autosome), unlike the majority of genes along the sex chromosomes. Since individuals of either sex will receive two copies of every gene in a [[pseudoautosomal region]], no dosage compensation is needed for females, so it is postulated that these regions of DNA have evolved mechanisms to escape X-inactivation. The genes of pseudoautosomal regions of the Xi do not have the typical modifications of the Xi and have little Xist RNA bound.

The existence of genes along the inactive X which are not silenced explains the defects in humans with atypical numbers of the X chromosome, such as [[Turner syndrome]] (X0, caused by SHOX gene<ref>{{Cite web |title=Turner syndrome: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/turner-syndrome/ |access-date=10 February 2023 |website=medlineplus.gov |language=en}}</ref>) or [[Klinefelter syndrome]] (XXY). Theoretically, X-inactivation should eliminate the differences in gene dosage between affected individuals and individuals with a typical chromosome complement. In affected individuals, however, X-inactivation is incomplete and the dosage of these non-silenced genes will differ as they escape X-inactivation, similar to an autosomal [[aneuploidy]].

The precise mechanisms that control escape from X-inactivation are not known, but silenced and escape regions have been shown to have distinct chromatin marks.<ref name="Calabrese JM, Sun W, Song L, Mugford JW, Williams L, Yee D, Starmer J, Mieczkowski P, Crawford GE, Magnuson T 2012 951–63"/><ref>{{cite journal | vauthors = Berletch JB, Yang F, Disteche CM | title = Escape from X inactivation in mice and humans | journal = Genome Biology | volume = 11 | issue = 6 | pages = 213 | date = June 2010 | pmid = 20573260 | pmc = 2911101 | doi = 10.1186/gb-2010-11-6-213 | doi-access = free }}</ref> It has been suggested that escape from X-inactivation might be mediated by expression of [[long non-coding RNA]] (lncRNA) within the escaping chromosomal domains.<ref name="pmid21047393">{{cite journal | vauthors = Reinius B, Shi C, Hengshuo L, Sandhu KS, Radomska KJ, Rosen GD, Lu L, Kullander K, Williams RW, Jazin E | title = Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse | journal = BMC Genomics | volume = 11 | pages = 614 | date = November 2010 | pmid = 21047393 | pmc = 3091755 | doi = 10.1186/1471-2164-11-614 | doi-access = free }}</ref>