Rsx is a Metatherian RNA with Xist-like Properties in X-chromosome Inactivation

Overview

Journal Nature

Specialty Science

Date 2012 Jun 23

PMID 22722828

Citations 82

Authors

Jennifer Grant

Shantha K Mahadevaiah

Pavel Khil

Mahesh N Sangrithi

Helene Royo

Janine Duckworth

John R McCarrey

John L VandeBerg

Marilyn B Renfree

Willie Taylor

Greg Elgar

R Daniel Camerini-Otero

Mike J Gilchrist

James M A Turner

Affiliations

Soon will be listed here.

Abstract

In female (XX) mammals, one of the two X chromosomes is inactivated to ensure an equal dose of X-linked genes with males (XY). X-chromosome inactivation in eutherian mammals is mediated by the non-coding RNA Xist. Xist is not found in metatherians (marsupials), and how X-chromosome inactivation is initiated in these mammals has been the subject of speculation for decades. Using the marsupial Monodelphis domestica, here we identify Rsx (RNA-on-the-silent X), an RNA that has properties consistent with a role in X-chromosome inactivation. Rsx is a large, repeat-rich RNA that is expressed only in females and is transcribed from, and coats, the inactive X chromosome. In female germ cells, in which both X chromosomes are active, Rsx is silenced, linking Rsx expression to X-chromosome inactivation and reactivation. Integration of an Rsx transgene on an autosome in mouse embryonic stem cells leads to gene silencing in cis. Our findings permit comparative studies of X-chromosome inactivation in mammals and pose questions about the mechanisms by which X-chromosome inactivation is achieved in eutherians.

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References

Mahadevaiah S, Royo H, VandeBerg J, McCarrey J, Mackay S, Turner J . Key features of the X inactivation process are conserved between marsupials and eutherians. Curr Biol. 2009; 19(17):1478-84. DOI: 10.1016/j.cub.2009.07.041. View

de Napoles M, Nesterova T, Brockdorff N . Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells. PLoS One. 2007; 2(9):e860. PMC: 1959243. DOI: 10.1371/journal.pone.0000860. View

Penny G, Kay G, Sheardown S, Rastan S, Brockdorff N . Requirement for Xist in X chromosome inactivation. Nature. 1996; 379(6561):131-7. DOI: 10.1038/379131a0. View

Kohlmaier A, Savarese F, Lachner M, Martens J, Jenuwein T, Wutz A . A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol. 2004; 2(7):E171. PMC: 449785. DOI: 10.1371/journal.pbio.0020171. View

Chaumeil J, Waters P, Koina E, Gilbert C, Robinson T, Marshall Graves J . Evolution from XIST-independent to XIST-controlled X-chromosome inactivation: epigenetic modifications in distantly related mammals. PLoS One. 2011; 6(4):e19040. PMC: 3081832. DOI: 10.1371/journal.pone.0019040. View

Lyon M . Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961; 190:372-3. DOI: 10.1038/190372a0. View

Lee J, Jaenisch R . Long-range cis effects of ectopic X-inactivation centres on a mouse autosome. Nature. 1997; 386(6622):275-9. DOI: 10.1038/386275a0. View

Nilsson M, Churakov G, Sommer M, van Tran N, Zemann A, Brosius J . Tracking marsupial evolution using archaic genomic retroposon insertions. PLoS Biol. 2010; 8(7):e1000436. PMC: 2910653. DOI: 10.1371/journal.pbio.1000436. View

Heard E, Mongelard F, Arnaud D, Chureau C, Vourch C, Avner P . Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells. Proc Natl Acad Sci U S A. 1999; 96(12):6841-6. PMC: 22003. DOI: 10.1073/pnas.96.12.6841. View

10.

Plath K, Fang J, Mlynarczyk-Evans S, Cao R, Worringer K, Wang H . Role of histone H3 lysine 27 methylation in X inactivation. Science. 2003; 300(5616):131-5. DOI: 10.1126/science.1084274. View

11.

Rens W, Wallduck M, Lovell F, Ferguson-Smith M, Ferguson-Smith A . Epigenetic modifications on X chromosomes in marsupial and monotreme mammals and implications for evolution of dosage compensation. Proc Natl Acad Sci U S A. 2010; 107(41):17657-62. PMC: 2955130. DOI: 10.1073/pnas.0910322107. View

12.

Chuva de Sousa Lopes S, Hayashi K, Shovlin T, Mifsud W, Surani M, Mclaren A . X chromosome activity in mouse XX primordial germ cells. PLoS Genet. 2008; 4(2):e30. PMC: 2233679. DOI: 10.1371/journal.pgen.0040030. View

13.

Brockdorff N, Ashworth A, Kay G, Cooper P, Smith S, McCabe V . Conservation of position and exclusive expression of mouse Xist from the inactive X chromosome. Nature. 1991; 351(6324):329-31. DOI: 10.1038/351329a0. View

14.

Silva J, Mak W, Zvetkova I, Appanah R, Nesterova T, Webster Z . Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Dev Cell. 2003; 4(4):481-95. DOI: 10.1016/s1534-5807(03)00068-6. View

15.

Hasegawa Y, Brockdorff N, Kawano S, Tsutui K, Tsutui K, Nakagawa S . The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Dev Cell. 2010; 19(3):469-76. DOI: 10.1016/j.devcel.2010.08.006. View

16.

Lee J, Strauss W, Dausman J, Jaenisch R . A 450 kb transgene displays properties of the mammalian X-inactivation center. Cell. 1996; 86(1):83-94. DOI: 10.1016/s0092-8674(00)80079-3. View

17.

Brown C, Hendrich B, Rupert J, Lafreniere R, Xing Y, Lawrence J . The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell. 1992; 71(3):527-42. DOI: 10.1016/0092-8674(92)90520-m. View

18.

Deakin J, Chaumeil J, Hore T, Marshall Graves J . Unravelling the evolutionary origins of X chromosome inactivation in mammals: insights from marsupials and monotremes. Chromosome Res. 2009; 17(5):671-85. DOI: 10.1007/s10577-009-9058-6. View

19.

Brown C, Ballabio A, Rupert J, Lafreniere R, Grompe M, Tonlorenzi R . A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991; 349(6304):38-44. DOI: 10.1038/349038a0. View

20.

Duret L, Chureau C, Samain S, Weissenbach J, Avner P . The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science. 2006; 312(5780):1653-5. DOI: 10.1126/science.1126316. View