Abstract
The Polycomb group (PcG) encodes an evolutionarily conserved set of chromatin-modifying proteins that are thought to maintain cellular transcriptional memory by stably silencing gene expression. In mouse embryos that are mutated for the PcG protein Eed, X-chromosome inactivation (XCI) is not stably maintained in extra-embryonic tissues. Eed is a component of a histone-methyltransferase complex that is thought to contribute to stable silencing in undifferentiated cells due to its enrichment on the inactive X-chromosome in cells of the early mouse embryo and in stem cells of the extra-embryonic trophectoderm lineage. Here, we demonstrate that the inactive X-chromosome in Eed(-/-) trophoblast stem cells and in cells of the trophectoderm-derived extra-embryonic ectoderm in Eed(-/-) embryos remain transcriptionally silent, despite lacking the PcG-mediated histone modifications that normally characterize the facultative heterochromatin of the inactive X-chromosome. Whereas undifferentiated Eed(-/-) trophoblast stem cells maintained XCI, reactivation of the inactive X-chromosome occurred when these cells were differentiated. These results indicate that PcG complexes are not necessary to maintain transcriptional silencing of the inactive X-chromosome in undifferentiated stem cells. Instead, PcG proteins seem to propagate cellular memory by preventing transcriptional activation of facultative heterochromatin during differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CDX2 Transcription Factor
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Cell Differentiation / genetics*
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Cell Line
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Cells, Cultured
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Ectoderm / metabolism
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Embryo, Mammalian / metabolism
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Endoderm / metabolism
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Enhancer of Zeste Homolog 2 Protein
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Epigenesis, Genetic
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Gene Expression / genetics
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Heterochromatin / metabolism
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Histone-Lysine N-Methyltransferase
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Histones / metabolism
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Homeodomain Proteins / metabolism
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In Situ Hybridization, Fluorescence
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Methylation
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Mice
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Mice, Knockout
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Mice, Transgenic
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Polycomb Repressive Complex 2
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Polycomb-Group Proteins
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Proteins / metabolism
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RNA, Long Noncoding
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RNA, Untranslated / genetics
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RNA, Untranslated / metabolism
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Receptor, Fibroblast Growth Factor, Type 2 / genetics
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Repressor Proteins / physiology*
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T-Box Domain Proteins / genetics
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Transcription Factors / metabolism
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Trophoblasts / metabolism
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X Chromosome / genetics*
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X Chromosome / metabolism
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X Chromosome Inactivation*
Substances
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CDX2 Transcription Factor
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Cdx2 protein, mouse
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Eed protein, mouse
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Eomes protein, mouse
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Heterochromatin
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Histones
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Homeodomain Proteins
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Phc2 protein, mouse
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Polycomb-Group Proteins
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Proteins
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RNA, Long Noncoding
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RNA, Untranslated
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Repressor Proteins
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Suz12 protein, mouse
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T-Box Domain Proteins
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Transcription Factors
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Tsix transcript, mouse
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XIST non-coding RNA
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Green Fluorescent Proteins
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Enhancer of Zeste Homolog 2 Protein
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Ezh2 protein, mouse
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Histone-Lysine N-Methyltransferase
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Polycomb Repressive Complex 2
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Receptor, Fibroblast Growth Factor, Type 2