Editing Barr body (section)

==Mechanism==
All individuals with two X chromosomes (such as the majority of [[human]] females) possesses only one Barr body per [[somatic cell]], while all individuals with one X chromosome (such as most human males) have none.

The Barr body allows for equal expression of X chromosomes in the majority of human males and females.<ref>{{Cite journal |last1=Chow |first1=Jennifer |last2=Yen |first2=Ziny |last3=Ziesche |first3=Sonia |last4=Brown |first4=Carolyn |title=Silencing of the Mammalian X Chromosome |url=https://www.annualreviews.org/content/journals/10.1146/annurev.genom.6.080604.162350 |journal=Annual Reviews |date=2005 |volume=6 |pages=69–92|doi=10.1146/annurev.genom.6.080604.162350 |pmid=16124854 }}</ref> If X inactivation did not occur, females (XX) would be expressing two X chromosomes, and males (XY) would only be expressing one. The disappearance of a Barr body in females (expressing both X chromosomes) can result in misregulation of [[heterochromatin]]. This misregulation leaves the potential of [[Epigenetics|epigenetic]] instability and irregular [[gene expression]].<ref>{{Cite journal |last1=Sharma |first1=Deepti |last2=Koshy |first2=George |last3=Gupta |first3=Shruti |last4=Sharma |first4=Bhushan |last5=Grover |first5=Sonal |date=2018-01-10 |title=Deciphering the Role of the Barr Body in Malignancy: An insight into head and neck cancer |url=https://doi.org/10.18295/squmj.2017.17.04.003 |journal=Sultan Qaboos University Medical Journal  |volume=17 |issue=4 |pages=e389–e397 |doi=10.18295/squmj.2017.17.04.003 |pmid=29372079 |pmc=5766293 |issn=2075-0528}}</ref> Autosomal genes can be silenced when there is translocation of the X inactivation complex on the X chromosome to an [[autosome]].<ref name=":02">{{Cite journal |last1=Cotton |first1=Allison M. |last2=Chen |first2=Chih-Yu |last3=Lam |first3=Lucia L. |last4=Wasserman |first4=Wyeth W. |last5=Kobor |first5=Michael S. |last6=Brown |first6=Carolyn J. |date=2013-10-24 |title=Spread of X-chromosome inactivation into autosomal sequences: role for DNA elements, chromatin features and chromosomal domains |url=https://doi.org/10.1093/hmg/ddt513 |journal=Human Molecular Genetics |volume=23 |issue=5 |pages=1211–1223 |doi=10.1093/hmg/ddt513 |pmid=24158853 |pmc=4051349 |issn=1460-2083}}</ref>

Mammalian [[X-chromosome inactivation]] is initiated from the X inactivation centre or ''Xic'', usually found near the [[centromere]].<ref name="Rougeulle">{{cite journal | last1 = Rougeulle | first1 = C. | last2 = Avner | first2 = P. | year = 2003 | title = Controlling X-inactivation in mammals: what does the centre hold? | journal = Seminars in Cell & Developmental Biology| volume = 14 | issue = 6| pages = 331–340 | doi = 10.1016/j.semcdb.2003.09.014 | pmid = 15015740 }}</ref> The centre contains twelve [[gene]]s, seven of which code for [[protein]]s and five for untranslated [[RNA]]s. From the untranslated RNAs, only two are known to play an active role in the X inactivation process, ''[[Xist]]'' and ''[[Tsix]]''.<ref name="Rougeulle" /> The centre also appears to be important in chromosome counting: ensuring that random inactivation only takes place when two or more X-chromosomes are present. The provision of an extra artificial ''Xic'' in early [[embryogenesis]] can induce inactivation of the single X found in male cells.<ref name="Rougeulle" />

The roles of ''Xist'' and ''Tsix'' appear to be antagonistic. The loss of ''Tsix'' expression on the future inactive X chromosome results in an increase in levels of ''Xist'' around the ''Xic''. Meanwhile, on the future active X ''Tsix'' levels are maintained; thus the levels of ''Xist'' remain low.<ref>{{cite journal | last1 = Lee | first1 = J. T. | last2 = Davidow | first2 = L. S. | last3 = Warshawsky | first3 = D. | s2cid = 30636065 | year = 1999 | title = Tisx, a gene antisense to Xist at the X-inactivation centre | journal = Nat. Genet. | volume = 21 | issue = 4| pages = 400–404 | doi = 10.1038/7734 | pmid = 10192391 }}</ref> This shift allows ''Xist'' to begin coating the future inactive chromosome, spreading out from the ''Xic''.<ref name="lyon2003"/> In non-random inactivation this choice appears to be fixed and current evidence suggests that the maternally inherited [[gene]] may be [[Genomic Imprinting|imprinted]].<ref name="Full Text PDF"/> Variations in Xi frequency have been reported with age, pregnancy, the use of oral contraceptives, fluctuations in menstrual cycle and [[Neoplasm|neoplasia]].<ref>{{cite journal |last1=Sharma |first1=Deepti |title=Deciphering the Role of the Barr Body in Malignancy |journal=Sultan Qaboos University Medical Journal |date=January 10, 2018 |volume=17 |issue=4 |pages=389–397 |pmc=5766293 |pmid=29372079 |doi=10.18295/squmj.2017.17.04.003 }}</ref>

It is thought that this constitutes the mechanism of choice, and allows downstream processes to establish the compact state of the Barr body. These changes include [[histone]] modifications, such as histone H3 [[methylation]] (i.e. [[H3K27me3]] by [[Polycomb recruitment in X chromosome inactivation|PRC2 which is recruited by Xist]])<ref>{{cite journal | last1 = Heard | first1 = E. | last2 = Rougeulle | first2 = C. | last3 = Arnaud | first3 = D. | last4 = Avner | first4 = P. | last5 = Allis | first5 = C. D. | s2cid = 10124177 | year = 2001 | title = Methylation of Histone H3 at Lys-9 Is an Early Mark on the X Chromosome during X Inactivation | journal = Cell | volume = 107 | issue = 6| pages = 727–738 | doi = 10.1016/S0092-8674(01)00598-0 | pmid = 11747809 | doi-access = free }}</ref> and histone H2A [[ubiquitination]],<ref>{{cite journal | last1 = de Napoles | first1 = M. | last2 = Mermoud | first2 = J.E. | last3 = Wakao | first3 = R. | last4 = Tang | first4 = Y.A. | last5 = Endoh | first5 = M. | last6 = Appanah | first6 = R. | last7 = Nesterova | first7 = T.B. | last8 = Silva | first8 = J. | last9 = Otte | first9 = A.P. | last10 = Vidal | first10 = M. | last11 = Koseki | first11 = H. | last12 = Brockdorff | first12 = N. | year = 2004 | title = Polycomb Group Proteins Ring1A/B Link Ubiquitylation of Histone H2A to Heritable Gene Silencing and X Inactivation | journal = Dev. Cell | volume = 7 | issue = 5| pages = 663–676 | doi = 10.1016/j.devcel.2004.10.005 | pmid = 15525528 | doi-access = free }}</ref> as well as direct modification of the [[DNA]] itself, via the methylation of [[CpG site]]s.<ref>{{cite journal | last1 = Chadwick | first1 = B.P. | last2 = Willard | first2 = H.F. | year = 2003 | title = Barring gene expression after XIST: maintaining faculative heterochromatin on the inactive X. | journal = Seminars in Cell & Developmental Biology| volume = 14 | issue = 6| pages = 359–367 | doi = 10.1016/j.semcdb.2003.09.016 | pmid = 15015743 }}</ref> These changes help inactivate [[gene]] expression on the inactive X-chromosome and to bring about its compaction to form the Barr body. 3D reconstructions and microscopic analyses of the Barr body using [[chromosome painting]] have found that it has a smoother and rounder morphology than [[Autosome|autosomes]] and the active X chromosome, though it is similar in size to the latter, suggesting its chromatin is only slightly more condensed.<ref name=":10" />