Mammals compensate X chromosome gene dosage between the sexes by silencing of one of the two female X chromosomes. X inactivation is initiated in the early embryo and requires the non-coding Xist RNA, which encompasses the inactive X chromosome (Xi) and triggers its silencing. In differentiated cells, several factors including the histone variant macroH2A and the scaffold attachment factor SAF-A are recruited to the Xi and maintain its repression. Consequently, in female somatic cells the Xi remains stably silenced independently of Xist. Here, we identify the Trithorax group protein Ash2l as a novel component of the Xi. Ash2l is recruited by Xist concomitantly with Saf-A and macroH2A at the transition to Xi maintenance. Recruitment of these factors characterizes a developmental transition point for the chromatin composition of the Xi. Surprisingly, expression of a mutant Xist RNA that does not cause gene repression can trigger recruitment of Ash2l, Saf-A and macroH2A to the X chromosome, and can cause chromosome-wide histone H4 hypoacetylation. This suggests that a chromatin configuration is established on non-genic chromatin on the Xi by Xist to provide a repressive compartment that could be used for maintaining gene silencing. Gene silencing is mechanistically separable from the formation of this repressive compartment and, thus, requires additional pathways. This observation highlights a crucial role for spatial organization of chromatin changes in the maintenance of X inactivation.
机构:
Walter & Eliza Hall Inst Med Res, Div Mol Med, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic 3050, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Blewitt, Marnie E.
Gendrel, Anne-Valerie
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机构:
Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, MRC, Fac Med, London SW7 2AZ, EnglandQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Gendrel, Anne-Valerie
Pang, Zhenyi
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机构:
Queensland Inst Med Res, Brisbane, Qld 4006, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Pang, Zhenyi
Sparrow, Duncan B.
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h-index: 0
机构:
Univ New S Wales, Victor Chang Cardiac Res Inst, Sydney, NSW 2010, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Sparrow, Duncan B.
Whitelaw, Nadia
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h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Univ Queensland, Sch Med, Brisbane, Qld 4072, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Whitelaw, Nadia
Craig, Jeffrey M.
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h-index: 0
机构:
Murdoch Childrens Res Inst, Parkville, Vic 3052, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Craig, Jeffrey M.
Apedaile, Anwyn
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h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, MRC, Fac Med, London SW7 2AZ, EnglandQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Apedaile, Anwyn
Hilton, Douglas J.
论文数: 0引用数: 0
h-index: 0
机构:
Walter & Eliza Hall Inst Med Res, Div Mol Med, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic 3050, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Hilton, Douglas J.
Dunwoodie, Sally L.
论文数: 0引用数: 0
h-index: 0
机构:Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Dunwoodie, Sally L.
Brockdorff, Neil
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, MRC, Fac Med, London SW7 2AZ, EnglandQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Brockdorff, Neil
Kay, Graham F.
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h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Kay, Graham F.
Whitelaw, Emma
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h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
Chaumeil, J
Okamoto, I
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h-index: 0
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
Okamoto, I
Guggiari, M
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h-index: 0
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
Guggiari, M
Heard, E
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h-index: 0
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
Clemson, CM
McNeil, JA
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CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
McNeil, JA
Willard, HF
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h-index: 0
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
Willard, HF
Lawrence, JB
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h-index: 0
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
机构:
Walter & Eliza Hall Inst Med Res, Div Mol Med, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic 3050, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Blewitt, Marnie E.
Gendrel, Anne-Valerie
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, MRC, Fac Med, London SW7 2AZ, EnglandQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Gendrel, Anne-Valerie
Pang, Zhenyi
论文数: 0引用数: 0
h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Pang, Zhenyi
Sparrow, Duncan B.
论文数: 0引用数: 0
h-index: 0
机构:
Univ New S Wales, Victor Chang Cardiac Res Inst, Sydney, NSW 2010, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Sparrow, Duncan B.
Whitelaw, Nadia
论文数: 0引用数: 0
h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Univ Queensland, Sch Med, Brisbane, Qld 4072, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Whitelaw, Nadia
Craig, Jeffrey M.
论文数: 0引用数: 0
h-index: 0
机构:
Murdoch Childrens Res Inst, Parkville, Vic 3052, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Craig, Jeffrey M.
Apedaile, Anwyn
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, MRC, Fac Med, London SW7 2AZ, EnglandQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Apedaile, Anwyn
Hilton, Douglas J.
论文数: 0引用数: 0
h-index: 0
机构:
Walter & Eliza Hall Inst Med Res, Div Mol Med, Melbourne, Vic 3050, Australia
Univ Melbourne, Dept Med Biol, Melbourne, Vic 3050, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Hilton, Douglas J.
Dunwoodie, Sally L.
论文数: 0引用数: 0
h-index: 0
机构:Queensland Inst Med Res, Brisbane, Qld 4006, Australia
Dunwoodie, Sally L.
Brockdorff, Neil
论文数: 0引用数: 0
h-index: 0
机构:
Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, MRC, Fac Med, London SW7 2AZ, EnglandQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Brockdorff, Neil
Kay, Graham F.
论文数: 0引用数: 0
h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
Kay, Graham F.
Whitelaw, Emma
论文数: 0引用数: 0
h-index: 0
机构:
Queensland Inst Med Res, Brisbane, Qld 4006, AustraliaQueensland Inst Med Res, Brisbane, Qld 4006, Australia
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
Chaumeil, J
Okamoto, I
论文数: 0引用数: 0
h-index: 0
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
Okamoto, I
Guggiari, M
论文数: 0引用数: 0
h-index: 0
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
Guggiari, M
Heard, E
论文数: 0引用数: 0
h-index: 0
机构:
Inst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, FranceInst Curie, Mammalian Dev Epigenet Grp, CNRS, UMR 218, F-75248 Paris 05, France
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
Clemson, CM
McNeil, JA
论文数: 0引用数: 0
h-index: 0
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
McNeil, JA
Willard, HF
论文数: 0引用数: 0
h-index: 0
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA
Willard, HF
Lawrence, JB
论文数: 0引用数: 0
h-index: 0
机构:
CASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USACASE WESTERN RESERVE UNIV, DEPT GENET, CTR HUMAN GENET, CLEVELAND, OH 44106 USA