X-inactivation: Difference between revisions

Content deleted Content added
Monkbot (talk | contribs)
m Task 17: replace to-be-deprecated: |name-list-format= (3× replaced; usage: 3 of 3);
m fixed dashes using a script
Line 23:
=== Cycle of X-chromosome activation in rodents ===
The paragraphs below have to do only with rodents and do not reflect XI in the majority of mammals.
X-inactivation is part of the activation cycle of the X chromosome throughout the female life. The egg and the fertilized zygote initially use maternal transcripts, and the whole embryonic genome is silenced until zygotic genome activation. Thereafter, all mouse cells undergo an early, [[Imprinting (genetics)|imprinted]] inactivation of the paternally-derived X chromosome in [[mammalian embryogenesis|4-84–8 cell stage]] [[embryo]]s.<ref>{{cite journal | vauthors = Takagi N, Sasaki M | title = Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse | journal = Nature | volume = 256 | issue = 5519 | pages = 640–2 | date = August 1975 | pmid = 1152998 | doi = 10.1038/256640a0 | bibcode = 1975Natur.256..640T }}</ref><ref>{{cite journal | vauthors = Cheng MK, Disteche CM | title = Silence of the fathers: early X inactivation | journal = BioEssays | volume = 26 | issue = 8 | pages = 821–4 | date = August 2004 | pmid = 15273983 | doi = 10.1002/bies.20082 | url = http://www3.interscience.wiley.com/cgi-bin/fulltext/109565168/PDFSTART }}{{dead link|date=February 2019|bot=medic}}{{cbignore|bot=medic}}</ref><ref name="okamoto">{{cite journal | vauthors = Okamoto I, Otte AP, Allis CD, Reinberg D, Heard E | title = Epigenetic dynamics of imprinted X inactivation during early mouse development | journal = Science | volume = 303 | issue = 5658 | pages = 644–9 | date = January 2004 | pmid = 14671313 | doi = 10.1126/science.1092727 | bibcode = 2004Sci...303..644O }}</ref><ref name=":2">{{cite journal | vauthors = Deng Q, Ramsköld D, Reinius B, Sandberg R | title = Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells | journal = Science | volume = 343 | issue = 6167 | pages = 193–6 | date = January 2014 | pmid = 24408435 | doi = 10.1126/science.1245316 | bibcode = 2014Sci...343..193D }}</ref> The [[extraembryonic tissue]]s (which give rise to the [[placenta]] and other tissues supporting the embryo) retain this early imprinted inactivation, and thus only the maternal X chromosome is active in these tissues.
 
In the early [[blastocyst]], this initial, imprinted X-inactivation is reversed in the cells of the [[inner cell mass]] (which give rise to the embryo), and in these cells both X chromosomes become active again. Each of these cells then independently and randomly inactivates one copy of the X chromosome.<ref name=okamoto/> This inactivation event is irreversible during the lifetime of the individual, with the exception of the germline. In the female [[germline]] before meiotic entry, X-inactivation is reversed, so that after meiosis all haploid [[oocyte]]s contain a single active X chromosome.
Line 38:
# '''Xa<sup>M</sup>''' AND '''Xa<sup>P</sup>''' haploid germ cells (eggs).
 
The X activation cycle has been best studied in mice, but there are multiple studies in humans. As most of the evidence is coming from mice, the above scheme represents the events in mice. The completion of the meiosis is simplified here for clarity. Steps 1-41–4 can be studied in in vitro fertilized embryos, and in differentiating stem cells; X-reactivation happens in the developing embryo, and subsequent (6-76–7) steps inside the female body, therefore much harder to study.
 
===== Timing =====
Line 52:
|1
|Zygotic genome activation
|2-42–4 cell stage<ref name=":4">{{cite journal | vauthors = Xue Z, Huang K, Cai C, Cai L, Jiang CY, Feng Y, Liu Z, Zeng Q, Cheng L, Sun YE, Liu JY, Horvath S, Fan G | title = Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing | language = En | journal = Nature | volume = 500 | issue = 7464 | pages = 593–7 | date = August 2013 | pmid = 23892778 | pmc = 4950944 | doi = 10.1038/nature12364 | bibcode = 2013Natur.500..593X }}</ref>
|2-82–8 cell stage<ref name=":4" />
|-
|2
|Imprinted (paternal) X-inactivation
|4-84–8 cell stage<ref name=":2" /><ref name=":3">{{cite journal|vauthors=Borensztein M, Syx L, Ancelin K, Diabangouaya P, Picard C, Liu T, Liang JB, Vassilev I, Galupa R, Servant N, Barillot E, Surani A, Chen CJ, Heard E|date=March 2017|title=Xist-dependent imprinted X inactivation and the early developmental consequences of its failure|journal=Nature Structural & Molecular Biology|language=En|volume=24|issue=3|pages=226–233|doi=10.1038/nsmb.3365|pmc=5337400|pmid=28134930}}</ref>
|Unclear if it takes place in humans<ref name=":5">{{cite journal | vauthors = Deng X, Berletch JB, Nguyen DK, Disteche CM | title = X chromosome regulation: diverse patterns in development, tissues and disease | language = En | journal = Nature Reviews. Genetics | volume = 15 | issue = 6 | pages = 367–78 | date = June 2014 | pmid = 24733023 | pmc = 4117651 | doi = 10.1038/nrg3687 }}</ref>
|-
Line 117:
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) 155-159155–159.</ref>
 
===Silencing===