Epigenetic safeguards are coordinately removed to reverse cell identity [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA488063 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic safeguards are coordinately removed to reverse cell identity
| PRJNA488060 | ENA
Project description:Epigenetic safeguards are coordinately removed to reverse cell identity [5hmC Enrichment]
| PRJNA488064 | ENA
Project description:Epigenetic modifications operate in concert to maintain cell identity, yet how these interconnected networks suppress alternative cell fates remains unknown. Here we uncover a link between the removal of repressive histone H3K9 methylation and DNA methylation during the reprogramming of somatic cells to pluripotency. The H3K9me2 demethylase, Kdm3b, transcriptionally controls DNA demethylase Tet1 expression. Unexpectedly, in the absence of Kdm3b, loci that have to be DNA demethylated are trapped in an intermediate hydroxymethylated (5hmC) state and do not resolve to unmethylated cytosine. Ectopic 5hmC trapping precludes the chromatin association of master pluripotency factor, POU5F1, and pluripotent gene activation. Tet1 but not Tet2 is critical for this defining event in the reprogramming process. Taken together we uncover a mechanism of coordinated chromatin modification removal in disrupting cell identity.
2019-09-26 | GSE119076 | GEO
Project description:Epigenetic modifications operate in concert to maintain cell identity, yet how these interconnected networks suppress alternative cell fates remains unknown. Here we uncover a link between the removal of repressive histone H3K9 methylation and DNA methylation during the reprogramming of somatic cells to pluripotency. The H3K9me2 demethylase, Kdm3b, transcriptionally controls DNA demethylase Tet1 expression. Unexpectedly, in the absence of Kdm3b, loci that have to be DNA demethylated are trapped in an intermediate hydroxymethylated (5hmC) state and do not resolve to unmethylated cytosine. Ectopic 5hmC trapping precludes the chromatin association of master pluripotency factor, POU5F1, and pluripotent gene activation. Tet1 but not Tet2 is critical for this defining event in the reprogramming process. Taken together we uncover a mechanism of coordinated chromatin modification removal in disrupting cell identity.
2019-09-26 | GSE119075 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-09-26 | GSE119077 | GEO
Project description:The establishment and maintenance of cellular identity rely upon the precise coordination of regulatory pathways culminating to the proper execution of cell type-specific gene expression programs. Generation of induced pluripotent stem cells (iPSCs) from highly specialized cell types provides an excellent model system to study how cells maintain their stability through the functional interplay of transcription factors and chromatin structure, and how they can change identity, especially in the context of disease. Previous studies have shown that chromatin structure safeguards cell identity by acting as a barrier to reprogramming. Here, we investigated the mechanisms of how the histone variant macroH2A inhibits reprogramming by interfering with the mesenchyme to epithelial transition, a step that is a prerequisite for reprogramming of mouse embryonic fibroblasts. We found that each of the macroH2A isoforms regulates the expression of defined sets of genes, whose overall function is to stabilize the mesenchyme phenotype, thus resisting reprogramming. We identified a novel gene network (MSCN, mesenchyme network) composed of 63 macroH2A-regulated genes encoding proteins of the extracellular matrix, cell membrane, cytoplasmic signal integrators and the transcriptional regulators Id2 and Snai2, all of which can function as key controllers of the mesenchyme phenotype. Functional studies including ChIP-seq and KD experiments using any one of the individual macroH2A isoforms revealed an isoform-specific combinatorial targeting of the genes that reconstruct the MSCN. Our findings established that the combinatorial macroH2A targeting of the MSCN components safeguards cell identity and demonstrated its pivotal role in maintaining the differentiated cell phenotype by generating robustness in gene expression programs to resist cellular reprogramming.
2023-06-21 | GSE215883 | GEO
Project description:The establishment and maintenance of cellular identity rely upon the precise coordination of regulatory pathways culminating to the proper execution of cell type-specific gene expression programs. Generation of induced pluripotent stem cells (iPSCs) from highly specialized cell types provides an excellent model system to study how cells maintain their stability through the functional interplay of transcription factors and chromatin structure, and how they can change identity, especially in the context of disease. Previous studies have shown that chromatin structure safeguards cell identity by acting as a barrier to reprogramming. Here, we investigated the mechanisms of how the histone variant macroH2A inhibits reprogramming by interfering with the mesenchyme to epithelial transition, a step that is a prerequisite for reprogramming of mouse embryonic fibroblasts. We found that each of the macroH2A isoforms regulates the expression of defined sets of genes, whose overall function is to stabilize the mesenchyme phenotype, thus resisting reprogramming. We identified a novel gene network (MSCN, mesenchyme network) composed of 63 macroH2A-regulated genes encoding proteins of the extracellular matrix, cell membrane, cytoplasmic signal integrators and the transcriptional regulators Id2 and Snai2, all of which can function as key controllers of the mesenchyme phenotype. Functional studies including ChIP-seq and KD experiments using any one of the individual macroH2A isoforms revealed an isoform-specific combinatorial targeting of the genes that reconstruct the MSCN. Our findings established that the combinatorial macroH2A targeting of the MSCN components safeguards cell identity and demonstrated its pivotal role in maintaining the differentiated cell phenotype by generating robustness in gene expression programs to resist cellular reprogramming.
2023-06-21 | GSE215884 | GEO
Project description:DDX18 safeguards rDNA epigenetic landscape by counteracting PRC2 and maintains ESC identity
| PRJNA512533 | ENA
Project description:RUNX1 safeguards the identity of the fetal ovary through an interplay with FOXL2
| PRJNA529855 | ENA