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James Turner group

X chromosome inactivation, meiotic silencing and infertility

In mammals, X chromosome inactivation (XCI) occurs in all cells in the female and in developing germ cells in the male. In females, XCI serves to equalise X-dosage with males and abnormalities in this process cause various diseases, including mental retardation. The precise role of XCI in male germ cells is unclear, but defects lead to infertility. We study the mechanisms underlying both forms of XCI and the influence of XCI on the gene content of the X chromosome.

We have shown that XCI in the male occurs because the X chromosome has no pairing partner during meiosis. Furthermore this form of X-silencing requires the tumour suppressor BRCA1. We have found that male XCI drives amplification of genes involved in late spermatogenesis on the X chromosome, with 18% of X-linked genes being expressed exclusively in developing sperm. Recently, we have used a new model organism, the marsupial Monodelphis domestica, to trace the evolution of XCI in mammals. These studies showed that most of the molecular features of XCI arose very early in mammalian evolution.

Figure 1

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Localisation of BRCA1 to the X and Y chromosomes during male meiosis.

Figure 2

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The inactive X chromosome, labeled with H3K27-methylation, in female marsupial brain cells.

Research projects

Collaborators

Paul Burgoyne (NIMR)
Rita Cha (NIMR)
Robin Lovell-Badge (NIMR)
Allan Bradley (Sanger Center, Cambridge, UK)
Eric Brown (University of Pennsylvania School of Medicine, Philadelphia, USA)
Haruhiko Koseki (RIKEN Research Centre Yokamam, Japan)
Peter Warburton (Mount Sinai School of Medicine, NY, USA)

Selected publications

Mahadevaiah SK, Royo H, McCarrey JR, VandeBerg JL, Mackay S and Turner JM (2009)
Key features of the X inactivation process are conserved between marsupials and eutherians.
Current Biology 19, 1478-84 PubMed abstract
Mueller, JL; Mahadevaiah, SK; Park, PJ; Warburton, PE; Page, DC and Turner, JMA (2008)
The mouse X chromosome is enriched for multicopy testis genes showing postmeiotic expression.
Nature Genetics 40, 794-9 PubMed abstract
Turner JMA, Mahadevaiah SK, Fernandez-Capetillo O, Nussenzweig A, Xu X, Deng CX and Burgoyne PS (2005)
Silencing of unsynapsed meiotic chromosomes in the mouse.
Nature Genetics 37, 41-47 PubMed abstract