학술논문

The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation
Document Type
article
Source
Nature Cell Biology. 8(2)
Subject
Biochemistry and Cell Biology
Biological Sciences
Stem Cell Research
Genetics
Stem Cell Research - Embryonic - Non-Human
Underpinning research
1.1 Normal biological development and functioning
Generic health relevance
Animals
CDX2 Transcription Factor
Cell Differentiation
Cell Line
Cells
Cultured
Ectoderm
Embryo
Mammalian
Endoderm
Enhancer of Zeste Homolog 2 Protein
Epigenesis
Genetic
Gene Expression
Green Fluorescent Proteins
Heterochromatin
Histone-Lysine N-Methyltransferase
Histones
Homeodomain Proteins
In Situ Hybridization
Fluorescence
Methylation
Mice
Mice
Knockout
Mice
Transgenic
Polycomb Repressive Complex 2
Polycomb-Group Proteins
Proteins
RNA
Long Noncoding
RNA
Untranslated
Receptor
Fibroblast Growth Factor
Type 2
Repressor Proteins
T-Box Domain Proteins
Transcription Factors
Trophoblasts
X Chromosome
X Chromosome Inactivation
Medical and Health Sciences
Developmental Biology
Biochemistry and cell biology
Language
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.