Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA
Copyright policy )Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA
AbstractPseudogene-derived, long non-coding RNAs (lncRNAs) act as epigenetic regulators of gene expression. Here we present a panel of new mouseOct4pseudogenes and demonstrate that the X-linkedOct4pseudogeneOct4P4critically impacts mouse embryonic stem cells (mESCs) self-renewal. SenseOct4P4transcription produces a spliced, nuclear-restricted lncRNA that is efficiently upregulated during mESC differentiation.Oct4P4lncRNA forms a complex with the SUV39H1 HMTase to direct the imposition of H3K9me3 and HP1α to the promoter of the ancestralOct4gene, located on chromosome 17, leading to gene silencing and reduced mESC self-renewal. TargetingOct4P4expression in primary mouse embryonic fibroblasts causes the re-acquisition of self-renewing features of mESC. We demonstrate thatOct4P4lncRNA plays an important role in inducing and maintaining silencing of the ancestralOct4gene in differentiating mESCs. Our data introduces a sense pseudogene–lncRNA-based mechanism of epigenetic gene regulation that controls the cross-talk between pseudogenes and their ancestral genes.
- University of Udine Italy
- University of Trieste Italy
- AREA Science Park Italy
- Spanish National Cancer Research Centre Spain
Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, Article, Cell Line, Epigenesis, Genetic, Histones, Pseudogene, Mice, Cell Line, Tumor, Animals, Immunoprecipitation, Cell Self Renewal, Methyltransferase, NIH 3T3 Cell, Animal, Gene Expression Regulation, Developmental, Mouse Embryonic Stem Cell, Mouse Embryonic Stem Cells, Methyltransferases, Repressor Protein, Animals; Cell Line; Cell Line, Tumor; Cell Self Renewal; Chromatin Immunoprecipitation; Chromosomal Proteins, Non-Histone; Epigenesis, Genetic; Histones; Immunoprecipitation; Methyltransferases; Mice; Mouse Embryonic Stem Cells; NIH 3T3 Cells; Octamer Transcription Factor-3; Pseudogenes; RNA, Long Noncoding; Repressor Proteins; Gene Expression Regulation, Developmental, Repressor Proteins, Histone, Chromobox Protein Homolog 5, Biochemistry, Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all), NIH 3T3 Cells, RNA, Long Noncoding, Octamer Transcription Factor-3, Pseudogenes
Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, Article, Cell Line, Epigenesis, Genetic, Histones, Pseudogene, Mice, Cell Line, Tumor, Animals, Immunoprecipitation, Cell Self Renewal, Methyltransferase, NIH 3T3 Cell, Animal, Gene Expression Regulation, Developmental, Mouse Embryonic Stem Cell, Mouse Embryonic Stem Cells, Methyltransferases, Repressor Protein, Animals; Cell Line; Cell Line, Tumor; Cell Self Renewal; Chromatin Immunoprecipitation; Chromosomal Proteins, Non-Histone; Epigenesis, Genetic; Histones; Immunoprecipitation; Methyltransferases; Mice; Mouse Embryonic Stem Cells; NIH 3T3 Cells; Octamer Transcription Factor-3; Pseudogenes; RNA, Long Noncoding; Repressor Proteins; Gene Expression Regulation, Developmental, Repressor Proteins, Histone, Chromobox Protein Homolog 5, Biochemistry, Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all), NIH 3T3 Cells, RNA, Long Noncoding, Octamer Transcription Factor-3, Pseudogenes
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