Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

X-chromosome inactivation: a hypothesis linking ontogeny and phylogeny

Nature Reviews Genetics volume 6, pages 410–418 (2005)Cite this article

Abstract

In mammals, sex is determined by differential inheritance of a pair of dimorphic chromosomes: the gene-rich X chromosome and the gene-poor Y chromosome. To balance the unequal X-chromosome dosage between the XX female and XY male, mammals have adopted a unique form of dosage compensation in which one of the two X chromosomes is inactivated in the female. This mechanism involves a complex, highly coordinated sequence of events and is a very different strategy from those used by other organisms, such as the fruitfly and the worm. Why did mammals choose an inactivation mechanism when other, perhaps simpler, means could have been used? Recent data offer a compelling link between ontogeny and phylogeny. Here, we propose that X-chromosome inactivation and imprinting might have evolved from an ancient genome-defence mechanism that silences unpaired DNA.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Strategies of dosage compensation.
Figure 2: The ontogeny of X-chromosome inactivation in the mouse: two current views.
Figure 3: Paternal X-chromosome silencing from sperm to zygote.
Figure 4: Parallels through ontogeny and phylogeny.
Figure 5: Meiotic sex-chromosome inactivation by unpaired silencing in mammals.
Figure 6: A generalized model for how the nature of the dosage-compensation mechanism depends on the method of sex determination.

Similar content being viewed by others

References

  1. Graves, J. A. Mammals that break the rules: genetics of marsupials and monotremes. Annu. Rev. Genet. 30, 233–260 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Lahn, B. T. & Page, D. C. Functional coherence of the human Y chromosome. Science 278, 675–680 (1997).

    Article  CAS  PubMed  Google Scholar 

  3. Lahn, B. T., Pearson, N. M. & Jegalian, K. The human Y chromosome, in the light of evolution. Nature Rev. Genet. 2, 207–216 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Vallender, E. J. & Lahn, B. T. How mammalian sex chromosomes acquired their peculiar gene content. Bioessays 26, 159–169 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. Spatz, A., Borg, C. & Feunteun, J. X-chromosome genetics and human cancer. Nature Rev. Cancer 4, 617–629 (2004).

    Article  CAS  Google Scholar 

  6. Lyon, M. F. Gene action in the X chromosome of the mouse (Mus musculus). Nature 190, 372–373 (1961).

    Article  CAS  PubMed  Google Scholar 

  7. Avner, P. & Heard, E. X-chromosome inactivation: counting, choice and initiation. Nature Rev. Genet. 2, 59–67 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Brockdorff, N. et al. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell 71, 515–526 (1992).

    Article  CAS  PubMed  Google Scholar 

  9. Brown, C. J. et al. 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 71, 527–542 (1992).

    Article  CAS  PubMed  Google Scholar 

  10. Lee, J. T., Davidow, L. S. & Warshawsky, D. Tsix, a gene antisense to Xist at the X-inactivation centre. Nature Genet. 21, 400–404 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Ogawa, Y. & Lee, J. T. Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Mol. Cell 11, 731–743 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Lee, J. T. Disruption of imprinted X inactivation by parent-of-origin effects at Tsix. Cell 103, 17–27 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. Sado, T., Wang, Z., Sasaki, H. & Li, E. Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development 128, 1275–1286 (2001).

    CAS  PubMed  Google Scholar 

  14. Clemson, C. M., McNeil, J. A., Willard, H. F. & Lawrence, J. B. XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure. J. Cell Biol. 132, 259–275 (1996).

    Article  CAS  PubMed  Google Scholar 

  15. Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S. & Brockdorff, N. Requirement for Xist in X chromosome inactivation. Nature 379, 131–137 (1996).

    Article  CAS  PubMed  Google Scholar 

  16. Sharman, G. B. Late DNA replication in the paternally derived X chromosome of female kangaroos. Nature 230, 231–232 (1971).

    Article  CAS  PubMed  Google Scholar 

  17. Takagi, N. & Sasaki, M. Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature 256, 640–642 (1975).

    Article  CAS  PubMed  Google Scholar 

  18. Xue, F. et al. Aberrant patterns of X chromosome inactivation in bovine clones. Nature Genet. 31, 216–220 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Migeon, B. R. & Do, T. T. In search of non-random X inactivation: studies of fetal membranes heterozygous for glucose-6-phosphate dehydrogenase. Am. J. Hum. Genet. 31, 581–585 (1979).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Ropers, H. H., Wolff, G. & Hitzeroth, H. W. Preferential X inactivation in human placenta membranes: is the paternal X inactive in early embryonic development of female mammals? Hum. Genet. 43, 265–273 (1978).

    Article  CAS  PubMed  Google Scholar 

  21. Zeng, S. M. & Yankowitz, J. X-inactivation patterns in human embryonic and extra-embryonic tissues. Placenta 24, 270–275 (2003).

    Article  PubMed  Google Scholar 

  22. Cooper, D. W. Directed genetic change model for X chromosome inactivation in eutherian mammals. Nature 230, 292–294 (1971).

    Article  CAS  PubMed  Google Scholar 

  23. Marahrens, Y., Panning, B., Dausman, J., Strauss, W. & Jaenisch, R. Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes Dev. 11, 156–166 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Cline, T. W. & Meyer, B. J. Vive la difference: males vs females in flies vs worms. Annu. Rev. Genet. 30, 637–702 (1996).

    Article  CAS  PubMed  Google Scholar 

  25. Park, Y. & Kuroda, M. I. Epigenetic aspects of X-chromosome dosage compensation. Science 293, 1083–1085 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Takagi, N. Imprinted X-chromosome inactivation: enlightenment from embryos in vivo. Semin. Cell Dev. Biol. 14, 319–329 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Goto, T. & Monk, M. Regulation of X-chromosome inactivation in development in mice and humans. Microbiol. Mol. Biol. Rev. 62, 362–378 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Heard, E., Clerc, P. & Avner, P. X-chromosome inactivation in mammals. Annu. Rev. Genet. 31, 571–610 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. Lyon, M. F. X-chromosome inactivation and developmental patterns in mammals. Biol. Rev. Camb. Philos. Soc. 47, 1–35 (1972).

    Article  CAS  PubMed  Google Scholar 

  30. Adler, D. A., West, J. D. & Chapman, V. M. Expression of α-galactosidase in preimplantation mouse embryos. Nature 267, 838–839 (1977).

    Article  CAS  PubMed  Google Scholar 

  31. Gardner, R. L. & Lyon, M. F. X chromosome inactivation studied by injection of a single cell into the mouse blastocyst. Nature 231, 385–386 (1971).

    Article  CAS  PubMed  Google Scholar 

  32. Epstein, C. J., Smith, S., Travis, B. & Tucker, G. Both X chromosomes function before visible X-chromosome inactivation in female mouse embryos. Nature 274, 500–503 (1978).

    Article  CAS  PubMed  Google Scholar 

  33. Kratzer, P. G. & Gartler, S. M. HGPRT activity changes in preimplantation mouse embryos. Nature 274, 503–504 (1978).

    Article  CAS  PubMed  Google Scholar 

  34. Monk, M. & Harper, M. I. Sequential X chromosome inactivation coupled with cellular differentiation in early mouse embryos. Nature 281, 311–313 (1979).

    Article  CAS  PubMed  Google Scholar 

  35. Mukherjee, A. B. Cell cycle analysis and X-chromosome inactivation in the developing mouse. Proc. Natl Acad. Sci. USA 73, 1608–1611 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sugawara, O., Takagi, N. & Sasaki, M. Correlation between X-chromosome inactivation and cell differentiation in female preimplantation mouse embryos. Cytogenet. Cell Genet. 39, 210–219 (1985).

    Article  CAS  PubMed  Google Scholar 

  37. Latham, K. E. & Rambhatla, L. Expression of X-linked genes in androgenetic, gynogenetic, and normal mouse preimplantation embryos. Dev. Genet. 17, 212–222 (1995).

    Article  CAS  PubMed  Google Scholar 

  38. Matsui, J., Goto, Y. & Takagi, N. Control of Xist expression for imprinted and random X chromosome inactivation in mice. Hum. Mol. Genet. 10, 1393–1401 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Sheardown, S. A. et al. Stabilization of Xist RNA mediates initiation of X chromosome inactivation. Cell 91, 99–107 (1997).

    Article  CAS  PubMed  Google Scholar 

  40. Nesterova, T. B., Barton, S. C., Surani, M. A. & Brockdorff, N. Loss of Xist imprinting in diploid parthenogenetic preimplantation embryos. Dev. Biol. 235, 343–350 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Krietsch, W. K. et al. The expression of X-linked phosphoglycerate kinase in the early mouse embryo. Differentiation 23, 141–144 (1982).

    Article  CAS  PubMed  Google Scholar 

  42. Pravtcheva, D. D., Adra, C. N. & Ruddle, F. H. Timing of paternal Pgk-1 expression in embryos of transgenic mice. Development 111, 1109–1120 (1991).

    CAS  PubMed  Google Scholar 

  43. Huynh, K. D. & Lee, J. T. Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos. Nature 426, 857–862 (2003).

    Article  CAS  PubMed  Google Scholar 

  44. Okamoto, I., Otte, A. P., Allis, C. D., Reinberg, D. & Heard, E. Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 303, 644–649 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Brown, C. J. et al. Localization of the X inactivation centre on the human X chromosome in Xq13. Nature 349, 82–84 (1991).

    Article  CAS  PubMed  Google Scholar 

  46. Schultz, R. M. Regulation of zygotic gene activation in the mouse. Bioessays 15, 531–538 (1993).

    Article  CAS  PubMed  Google Scholar 

  47. Reik, W. & Walter, J. Genomic imprinting: parental influence on the genome. Nature Rev. Genet. 2, 21–32 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Lifschytz, E. & Lindsley, D. L. The role of X-chromosome inactivation during spermatogenesis. Proc. Natl Acad. Sci. USA 69, 182–186 (1972).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Lifschytz, E. & Lindsley, D. I. Sex chromosome activation during spermatogenesis. Genetics 78, 323–331 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Hoyer-Fender, S. Molecular aspects of XY body formation. Cytogenet. Genome Res. 103, 245–255 (2003).

    Article  CAS  PubMed  Google Scholar 

  51. McKee, B. D. & Handel, M. A. Sex chromosomes, recombination, and chromatin conformation. Chromosoma 102, 71–80 (1993).

    Article  CAS  PubMed  Google Scholar 

  52. Miklos, G. L. Sex-chromosome pairing and male fertility. Cytogenet. Cell Genet. 13, 558–577 (1974).

    Article  CAS  PubMed  Google Scholar 

  53. Lee, J. T. Sex chromosome inactivation: the importance of pairing. Curr. Biol. (in the press).

  54. Hendriksen, P. J. et al. Postmeiotic transcription of X and Y chromosomal genes during spermatogenesis in the mouse. Dev. Biol. 170, 730–733 (1995).

    Article  CAS  PubMed  Google Scholar 

  55. Khalil, A. M., Boyar, F. Z. & Driscoll, D. J. Dynamic histone modifications mark sex chromosome inactivation and reactivation during mammalian spermatogenesis. Proc. Natl Acad. Sci. USA 101, 16583–16587 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. McCarrey, J. R. et al. Differential transcription of Pgk genes during spermatogenesis in the mouse. Dev. Biol. 154, 160–168 (1992).

    Article  CAS  PubMed  Google Scholar 

  57. McCarrey, J. R., Dilworth, D. D. & Sharp, R. M. Semiquantitative analysis of X-linked gene expression during spermatogenesis in the mouse: ethidium-bromide staining of RT-PCR products. Genet. Anal. Tech. Appl. 9, 117–123 (1992).

    Article  CAS  PubMed  Google Scholar 

  58. McCarrey, J. R. et al. X-chromosome inactivation during spermatogenesis is regulated by an Xist/Tsix-independent mechanism in the mouse. Genesis 34, 257–266 (2002).

    Article  CAS  PubMed  Google Scholar 

  59. Singer-Sam, J., Robinson, M. O., Bellve, A. R., Simon, M. I. & Riggs, A. D. Measurement by quantitative PCR of changes in HPRT, PGK-1, PGK-2, APRT, MTase, and Zfy gene transcripts during mouse spermatogenesis. Nucleic Acids Res. 18, 1255–1259 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hendriksen, P. J. et al. Testis-specific expression of a functional retroposon encoding glucose-6-phosphate dehydrogenase in the mouse. Genomics 41, 350–359 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Ashworth, A., Skene, B., Swift, S. & Lovell-Badge, R. Zfa is an expressed retroposon derived from an alternative transcript of the Zfx gene. EMBO J. 9, 1529–1534 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Bradley, J. et al. An X-to-autosome retrogene is required for spermatogenesis in mice. Nature Genet. 36, 872–876 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Dahl, H. H., Brown, R. M., Hutchison, W. M., Maragos, C. & Brown, G. K. A testis-specific form of the human pyruvate dehydrogenase E1-α subunit is coded for by an intronless gene on chromosome 4. Genomics 8, 225–232 (1990).

    Article  CAS  PubMed  Google Scholar 

  64. McCarrey, J. R. & Thomas, K. Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 326, 501–505 (1987).

    Article  CAS  PubMed  Google Scholar 

  65. Emerson, J. J., Kaessmann, H., Betran, E. & Long, M. Extensive gene traffic on the mammalian X chromosome. Science 303, 537–540 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Wang, P. J. X chromosomes, retrogenes and their role in male reproduction. Trends Endocrinol. Metab. 15, 79–83 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Huynh, K. D. & Lee, J. T. Imprinted X inactivation in eutherians: a model of gametic execution and zygotic relaxation. Curr. Opin. Cell Biol. 13, 690–697 (2001).

    Article  CAS  PubMed  Google Scholar 

  68. Grutzner, F. et al. In the platypus a meiotic chain of ten sex chromosomes shares genes with the bird Z and mammal X chromosomes. Nature 432, 913–917 (2004).

    Article  CAS  PubMed  Google Scholar 

  69. Grutzner, F. & Graves, J. A. A platypus' eye view of the mammalian genome. Curr. Opin. Genet. Dev. 14, 642–649 (2004).

    Article  CAS  PubMed  Google Scholar 

  70. VandeBerg, J. L., Johnston, P. G., Cooper, D. W. & Robinson, E. S. X-chromosome inactivation and evolution in marsupials and other mammals. Isozymes Curr. Top. Biol. Med. Res. 9, 201–218 (1983).

    CAS  PubMed  Google Scholar 

  71. Lyon, M. F. Imprinting and X-chromosome inactivation. Results Probl. Cell Differ. 25, 73–90 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Shiu, P. K., Raju, N. B., Zickler, D. & Metzenberg, R. L. Meiotic silencing by unpaired DNA. Cell 107, 905–916 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Bean, C. J., Schaner, C. E. & Kelly, W. G. Meiotic pairing and imprinted X chromatin assembly in Caenorhabditis elegans. Nature Genet. 36, 100–105 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Turner, J. M. et al. BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation. Curr. Biol. 14, 2135–2142 (2004).

    Article  CAS  PubMed  Google Scholar 

  75. Turner, J. M. et al. Silencing of unsynapsed meiotic chromosomes in the mouse. Nature Genet. 37, 41–47 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Baarends, W. M. et al. Silencing of unpaired chromatin and histone H2A ubiquitination in mammalian meiosis. Mol. Cell. Biol. 25, 1041–1053 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lee, J. T. Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting? Curr. Biol. 13, R242–R254 (2003).

    Article  CAS  PubMed  Google Scholar 

  78. Turner, J. M. et al. Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist. J. Cell Sci. 115, 4097–4105 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Chadwick, B. P. & Willard, H. F. Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome. Proc. Natl Acad. Sci. USA 101, 17450–17455 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Charlesworth, B. The evolution of sex chromosomes. Science 251, 1030–1033 (1991).

    Article  CAS  PubMed  Google Scholar 

  81. Charlesworth, B. The evolution of chromosomal sex determination and dosage compensation. Curr. Biol. 6, 149–162 (1996).

    Article  CAS  PubMed  Google Scholar 

  82. Kelly, W. G. et al. X-chromosome silencing in the germline of C. elegans. Development 129, 479–492 (2002).

    CAS  PubMed  Google Scholar 

  83. Charlesworth, D. Plant sex determination and sex chromosomes. Heredity 88, 94–101 (2002).

    Article  PubMed  Google Scholar 

  84. Siroky, J., Castiglione, M. R. & Vyskot, B. DNA methylation patterns of Melandrium album chromosomes. Chromosome Res. 6, 441–446 (1998).

    Article  CAS  PubMed  Google Scholar 

  85. Vyskot, B., Siroky, J., Hladilova, R., Belyaev, N. D. & Turner, B. M. Euchromatic domains in plant chromosomes as revealed by H4 histone acetylation and early DNA replication. Genome 42, 343–350 (1999).

    Article  CAS  PubMed  Google Scholar 

  86. Lengerova, M., Moore, R. C., Grant, S. R. & Vyskot, B. The sex chromosomes of Silene latifolia revisited and revised. Genetics 165, 935–938 (2003).

    PubMed  PubMed Central  Google Scholar 

  87. McQueen, H. A., McBride, D., Miele, G., Bird, A. P. & Clinton, M. Dosage compensation in birds. Curr. Biol. 11, 253–257 (2001).

    Article  CAS  PubMed  Google Scholar 

  88. McCarrey, J. R. & Dilworth, D. D. Expression of Xist in mouse germ cells correlates with X-chromosome inactivation. Nature Genet. 2, 200–203 (1992).

    Article  CAS  PubMed  Google Scholar 

  89. Salido, E. C., Yen, P. H., Mohandas, T. K. & Shapiro, L. J. Expression of the X-inactivation-associated gene XIST during spermatogenesis. Nature Genet. 2, 196–199 (1992).

    Article  CAS  PubMed  Google Scholar 

  90. Richler, C., Soreq, H. & Wahrman, J. X inactivation in mammalian testis is correlated with inactive X-specific transcription. Nature Genet. 2, 192–195 (1992).

    Article  CAS  PubMed  Google Scholar 

  91. Singer-Sam, J., Chapman, V., LeBon, J. M. & Riggs, A. D. Parental imprinting studied by allele-specific primer extension after PCR: paternal X chromosome-linked genes are transcribed prior to preferential paternal X chromosome inactivation. Proc. Natl Acad. Sci. USA 89, 10469–10473 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Mak, W. et al. Reactivation of the paternal X chromosome in early mouse embryos. Science 303, 666–669 (2004).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all the members of our laboratory for insightful discussion and R. Spencer, S. Namekawa and M. Anguera for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Khanh D. Huynh & Jeannie T. Lee

Authors
  1. Khanh D. Huynh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeannie T. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeannie T. Lee.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

Entrez

Chic1

EED

EZH2

G6pd2

Pdha2

Pgk1

Pgk2

Tsix

Xist

Zfa

FURTHER INFORMATION

Jeannie Lee's web site

Glossary

ASYNAPSIS

Failure of chromosomes to pair during meiosis.

BLASTOCYST

An early stage of mammalian embryonic development at which the first cell lineages become established.

COT1 FISH

A technique to visualize nascent transcription that uses the Cot1 fraction of DNA that is rich in repetitive elements that often occur in introns and 3′ untranslated regions.

EPIBLAST

An embryonic lineage that is derived from the inner cell mass of the blastocyst, which gives rise to the body of the fetus.

EUTHERIANS

Mammals that give birth to live offspring (that is, they are viviparous) and possess an allantoic placenta — the allantois is the fetal membrane that facilitates nutrient and waste exchange between the fetus and the mother.

FLUORESCENCE IN SITU HYBRIDIZATION

A technique in which a fluorescently labelled DNA probe is used to detect a particular chromosome or gene with the help of fluorescence microscopy.

MEIOTIC CHECKPOINT

A surveillance mechanism specific to meiosis that ensures proper chromosome segregation.

PACHYTENE

The third phase of prophase I in meiosis.

THERIAN MAMMALS

A group of mammals that includes the eutherians and marsupials.

TROPHECTODERM

The outer layer of the blastocyst-stage embryo; the precursor to the bulk of the embryonic part of the placenta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huynh, K., Lee, J. X-chromosome inactivation: a hypothesis linking ontogeny and phylogeny. Nat Rev Genet 6, 410–418 (2005). https://doi.org/10.1038/nrg1604

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1604

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing