In male mammals, the X and Y chromosomes are transcriptionally silenced in primary spermatocytes by meiotic sex chromosome inactivation (MSCI) and remain repressed for the duration of spermatogenesis. Here, we test the longstanding hypothesis that disrupted MSCI might contribute to the preferential sterility of heterogametic hybrid males. We studied a cross between wild-derived inbred strains of Mus musculus musculus and M. m. domesticus in which sterility is asymmetric: F-1 males with a M. m. musculus mother are sterile or nearly so while F-1 males with a M. m. domesticus mother are normal. In previous work, we discovered widespread overexpression of X-linked genes in the testes of sterile but not fertile F-1 males. Here, we ask whether this overexpression is specifically a result of disrupted MSCI. To do this, we isolated cells from different stages of spermatogenesis and measured the expression of several genes using quantitative PCR. We found that X overexpression in sterile F-1 primary spermatocytes is coincident with the onset of MSCI and persists in postmeiotic spermatids. Using a series of recombinant X genotypes, we then asked whether X overexpression in hybrids is controlled by cis-acting loci across the X chromosome. We found that it is not. Instead, one large interval in the proximal portion of the M. m. musculus X chromosome is associated with both overexpression and the severity of sterility phenotypes in hybrids. These results demonstrate a strong association between X-linked hybrid male sterility and disruption of MSCI and suggest that transacting loci on the X are important for the transcriptional regulation of the X chromosome during spermatogenesis.
机构:
Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, EnglandNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Mahadevaiah, Shantha K.
;
Bourc'his, Deborah
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机构:
Inst Jacques Monod, INSERM U741, F-75251 Paris 05, FranceNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Bourc'his, Deborah
;
de Rooij, Dirk G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Ctr Reprod Med, NL-1105 AZ Amsterdam, Netherlands
Univ Utrecht, Fac Sci, Dept Endocrinol & Metab, NL-3584 CH Utrecht, NetherlandsNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
de Rooij, Dirk G.
;
Bestor, Timothy H.
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h-index: 0
机构:
Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USANatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Bestor, Timothy H.
;
Turner, James M. A.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, EnglandNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Turner, James M. A.
;
Burgoyne, Paul S.
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h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, EnglandNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
机构:
Univ Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, FranceUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
Montellier, Emilie
;
Rousseaux, Sophie
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机构:
Univ Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, FranceUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
Rousseaux, Sophie
;
Zhao, Yingming
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h-index: 0
机构:
Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USAUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
Zhao, Yingming
;
Khochbin, Saadi
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机构:
Univ Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, FranceUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
机构:
Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
MIT, Dept Biol, Cambridge, MA 02142 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Mueller, Jacob L.
;
Mahadevaiah, Shantha K.
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h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Res & Dev Genet, London NW7 1AA, EnglandWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Mahadevaiah, Shantha K.
;
Park, Peter J.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Partners Ctr Genet & Genom, Childrens Hosp Informat Program, Boston, MA 02115 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Park, Peter J.
;
Warburton, Peter E.
论文数: 0引用数: 0
h-index: 0
机构:
Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Warburton, Peter E.
;
Page, David C.
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
MIT, Dept Biol, Cambridge, MA 02142 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Page, David C.
;
Turner, James M. A.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Res & Dev Genet, London NW7 1AA, EnglandWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
机构:
Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, EnglandNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Mahadevaiah, Shantha K.
;
Bourc'his, Deborah
论文数: 0引用数: 0
h-index: 0
机构:
Inst Jacques Monod, INSERM U741, F-75251 Paris 05, FranceNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Bourc'his, Deborah
;
de Rooij, Dirk G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Ctr Reprod Med, NL-1105 AZ Amsterdam, Netherlands
Univ Utrecht, Fac Sci, Dept Endocrinol & Metab, NL-3584 CH Utrecht, NetherlandsNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
de Rooij, Dirk G.
;
Bestor, Timothy H.
论文数: 0引用数: 0
h-index: 0
机构:
Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USANatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Bestor, Timothy H.
;
Turner, James M. A.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, EnglandNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
Turner, James M. A.
;
Burgoyne, Paul S.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, EnglandNatl Inst Med Res, MRC, Div Stem Cell Biol & Dev Genet, London NW7 1AA, England
机构:
Univ Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, FranceUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
Montellier, Emilie
;
Rousseaux, Sophie
论文数: 0引用数: 0
h-index: 0
机构:
Univ Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, FranceUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
Rousseaux, Sophie
;
Zhao, Yingming
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USAUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
Zhao, Yingming
;
Khochbin, Saadi
论文数: 0引用数: 0
h-index: 0
机构:
Univ Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, FranceUniv Grenoble 1, INSERM, Inst Albert Bonniot, Fac Med,U823, La Tronche, France
机构:
Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
MIT, Dept Biol, Cambridge, MA 02142 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Mueller, Jacob L.
;
Mahadevaiah, Shantha K.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Res & Dev Genet, London NW7 1AA, EnglandWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Mahadevaiah, Shantha K.
;
Park, Peter J.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Partners Ctr Genet & Genom, Childrens Hosp Informat Program, Boston, MA 02115 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Park, Peter J.
;
Warburton, Peter E.
论文数: 0引用数: 0
h-index: 0
机构:
Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Warburton, Peter E.
;
Page, David C.
论文数: 0引用数: 0
h-index: 0
机构:
Whitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
MIT, Dept Biol, Cambridge, MA 02142 USAWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA
Page, David C.
;
Turner, James M. A.
论文数: 0引用数: 0
h-index: 0
机构:
Natl Inst Med Res, MRC, Div Stem Cell Res & Dev Genet, London NW7 1AA, EnglandWhitehead Inst, Howard Hughes Med Inst, Cambridge, MA 02142 USA