The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation.
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.
Kalantry
Sundeep
S
Department of Genetics and the Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC 27599-7264, USA.
Mills
Kyle C
KC
Yee
Della
D
Otte
Arie P
AP
Panning
Barbara
B
Magnuson
Terry
T
D000818:Animals; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D004475:Ectoderm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D004707:Endoderm / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011506:Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism; D014960:X Chromosome / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; C107275:Eed protein, mouse; C491198:Eomes protein, mouse; D006570:Heterochromatin; D006657:Histones; D018398:Homeodomain Proteins; C501292:Phc2 protein, mouse; D063146:Polycomb-Group Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C494163:Suz12 protein, mouse; D020825:T-Box Domain Proteins; D014157:Transcription Factors; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA; D049452:Green Fluorescent Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D051497:Receptor, Fibroblast Growth Factor, Type 2