Identification of TSIX, Encoding an RNA Antisense to Human XIST, Reveals Differences from Its Murine Counterpart: Implications for X Inactivation

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2001 Sep 14

PMID 11555794

Citations 50

Authors

B R MIGEON

A K Chowdhury

J A Dunston

I McIntosh

Affiliations

Soon will be listed here.

Abstract

X inactivation is the mammalian method for X-chromosome dosage compensation, but some features of this developmental process vary among mammals. Such species variations provide insights into the essential components of the pathway. Tsix encodes a transcript antisense to the murine Xist transcript and is expressed in the mouse embryo only during the initial stages of X inactivation; it has been shown to play a role in imprinted X inactivation in the mouse placenta. We have identified its counterpart within the human X inactivation center (XIC). Human TSIX produces a >30-kb transcript that is expressed only in cells of fetal origin; it is expressed from human XIC transgenes in mouse embryonic stem cells and from human embryoid-body-derived cells, but not from human adult somatic cells. Differences in the structure of human and murine genes indicate that human TSIX was truncated during evolution. These differences could explain the fact that X inactivation is not imprinted in human placenta, and they raise questions about the role of TSIX in random X inactivation.

Citing Articles

X-inactive-specific transcript: a long noncoding RNA with a complex role in sex differences in human disease.

Predescu D, Mokhlesi B, Predescu S Biol Sex Differ. 2024; 15(1):101.

PMID: 39639337 PMC: 11619133. DOI: 10.1186/s13293-024-00681-5.

Female-bias in systemic lupus erythematosus: How much is the X chromosome to blame?.

Vieira A, Almada-Correia I, Inacio J, Costa-Reis P, da Rocha S Biol Sex Differ. 2024; 15(1):76.

PMID: 39375734 PMC: 11460073. DOI: 10.1186/s13293-024-00650-y.

Dysregulation of the Long Noncoding RNA X-Inactive-Specific Transcript Expression in Male Patients with Pulmonary Arterial Hypertension.

Carman B, Qin S, Predescu D, Jana M, Cortese R, Aldred M Am J Pathol. 2024; 194(8):1592-1606.

PMID: 38705381 PMC: 11284765. DOI: 10.1016/j.ajpath.2024.04.005.

Mechanisms of sex differences in Alzheimer's disease.

Lopez-Lee C, Torres E, Carling G, Gan L Neuron. 2024; 112(8):1208-1221.

PMID: 38402606 PMC: 11076015. DOI: 10.1016/j.neuron.2024.01.024.

Silencing XIST on the future active X: Searching human and bovine preimplantation embryos for the repressor.

Aksit M, Yu B, Roelen B, Migeon B Eur J Hum Genet. 2022; 32(4):399-406.

PMID: 35585273 PMC: 10999447. DOI: 10.1038/s41431-022-01115-9.

References

Clemson C, McNeil J, Willard H, Lawrence J . XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J Cell Biol. 1996; 132(3):259-75. PMC: 2120729. DOI: 10.1083/jcb.132.3.259. View

MIGEON B, Kazi E, Hu J, Reeves R, Call L, Lawler A . Human X inactivation center induces random X chromosome inactivation in male transgenic mice. Genomics. 1999; 59(2):113-21. DOI: 10.1006/geno.1999.5861. View

Lyon M . Sex chromatin and gene action in the mammalian X-chromosome. Am J Hum Genet. 1962; 14:135-48. PMC: 1932279. View

Lyon M . X-chromosome inactivation. Pinpointing the centre. Nature. 1996; 379(6561):116-7. DOI: 10.1038/379116a0. View

Morey C, Arnaud D, Avner P, Clerc P . Tsix-mediated repression of Xist accumulation is not sufficient for normal random X inactivation. Hum Mol Genet. 2001; 10(13):1403-11. DOI: 10.1093/hmg/10.13.1403. View

van den Hurk J, Hendriks W, van de Pol D, Oerlemans F, Jaissle G, Ruther K . Mouse choroideremia gene mutation causes photoreceptor cell degeneration and is not transmitted through the female germline. Hum Mol Genet. 1997; 6(6):851-8. DOI: 10.1093/hmg/6.6.851. View

Mohandas T, Passage M, Williams 3rd J, Sparkes R, Yen P, Shapiro L . X-chromosome inactivation in cultured cells from human chorionic villi. Somat Cell Mol Genet. 1989; 15(2):131-6. DOI: 10.1007/BF01535073. View

Hong Y, Ontiveros S, Strauss W . A revision of the human XIST gene organization and structural comparison with mouse Xist. Mamm Genome. 2000; 11(3):220-4. DOI: 10.1007/s003350010040. View

Schwartz S, Zhang Z, Frazer K, Smit A, Riemer C, Bouck J . PipMaker--a web server for aligning two genomic DNA sequences. Genome Res. 2000; 10(4):577-86. PMC: 310868. DOI: 10.1101/gr.10.4.577. View

10.

MIGEON B, Do T . In search of nonrandom X inactivation: studies of the placenta from newborns heterozygous for glucose-6-phosphate dehydrogenase. Basic Life Sci. 1978; 12:379-91. DOI: 10.1007/978-1-4684-3390-6_26. View

11.

Lee J, Lu N . Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell. 1999; 99(1):47-57. DOI: 10.1016/s0092-8674(00)80061-6. View

12.

Milanesi L, DAngelo D, Rogozin I . GeneBuilder: interactive in silico prediction of gene structure. Bioinformatics. 1999; 15(7-8):612-21. DOI: 10.1093/bioinformatics/15.7.612. View

13.

MIGEON B, Wolf S, Axelman J, Kaslow D, Schmidt M . Incomplete X chromosome dosage compensation in chorionic villi of human placenta. Proc Natl Acad Sci U S A. 1985; 82(10):3390-4. PMC: 397781. DOI: 10.1073/pnas.82.10.3390. View

14.

Sado T, Wang Z, Sasaki H, Li E . Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development. 2001; 128(8):1275-86. DOI: 10.1242/dev.128.8.1275. View

15.

Shapiro M, Senapathy P . RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987; 15(17):7155-74. PMC: 306199. DOI: 10.1093/nar/15.17.7155. View

16.

Nesterova T, Slobodyanyuk S, Elisaphenko E, Shevchenko A, Johnston C, Pavlova M . Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. Genome Res. 2001; 11(5):833-49. PMC: 311126. DOI: 10.1101/gr.174901. View

17.

Simmler M, Cattanach B, Rasberry C, Rougeulle C, Avner P . Mapping the murine Xce locus with (CA)n repeats. Mamm Genome. 1993; 4(9):523-30. DOI: 10.1007/BF00364788. View

18.

MIGEON B, Winter H, Kazi E, Chowdhury A, Hughes A, Morrison H . Low-copy-number human transgene is recognized as an X inactivation center in mouse ES cells, but fails to induce cis-inactivation in chimeric mice. Genomics. 2001; 71(2):156-62. DOI: 10.1006/geno.2000.6421. View

19.

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

20.

Shamblott M, Axelman J, LITTLEFIELD J, Blumenthal P, Huggins G, Cui Y . Human embryonic germ cell derivatives express a broad range of developmentally distinct markers and proliferate extensively in vitro. Proc Natl Acad Sci U S A. 2001; 98(1):113-8. PMC: 14553. DOI: 10.1073/pnas.98.1.113. View