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PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation

ABSTRACT: PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation

PROVIDER: PRJNA350683 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4451730.fastq.gz	Fastqsanger.gz
	SRR4453260_1.fastq.gz	Fastqsanger.gz
	SRR4453260_2.fastq.gz	Fastqsanger.gz
	SRR4457840_1.fastq.gz	Fastqsanger.gz
	SRR4457840_2.fastq.gz	Fastqsanger.gz

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PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation [4C-seq]

Project description:Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology.

2017-02-11 | GSE89208 | GEO

PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation [ChIP-seq]

2017-02-11 | GSE89209 | GEO

PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation [RNA-seq EED]

2017-02-11 | GSE89210 | GEO

PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-11 | GSE89211 | GEO

Poised enhancers regulatory activity is topologically facilitated by polycomb [RNA-seq LHX5]

2017-10-26 | GSE89242 | GEO

H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers

Project description:Expression of histone H3.3K27M mutant proteins in diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and supports the proliferation of DIPG cells in part through silencing of tumor suppressor gene WT1.

2018-07-02 | GSE94834 | GEO

H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers

Project description:H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers

| PRJNA374553 | ENA

Mus musculus

Project description:PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation [4C-seq]

| PRJNA350733 | ENA

Mus musculus

Project description:PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation [ChIP-seq]

| PRJNA350689 | ENA

PRC2 shields naive pluripotent cells from trophectoderm and mesoderm differentiation [RNA-seq]

Project description:The first lineage choice made in human embryo development separates trophectoderm from the inner cell mass, which proceeds to form the pluripotent epiblast and primitive endoderm. Trophectoderm on the other hand gives rise to the placenta. Naïve pluripotent stem cells are derived from the pluripotent epiblast of the blastocyst and offer possibilities to explore how lineage integrity is maintained. Here, we discover that Polycomb repressive complex 2 (PRC2) restricts an intrinsic capacity of naïve pluripotent stem cells to give rise to trophectoderm. Through quantitative epigenome profiling, we find that broad histone H3 lysine 27 trimethylation (H3K27me3) hypermethylation is a common feature of naïve pluripotency across species. We define a previously unappreciated, naïve-specific set of bivalent promoters, featuring PRC2-mediated H3K27me3 concomitant with H3K4me3. Naïve bivalency maintains key trophectoderm transcription factors in a transcriptionally poised state that is resolved to an active state upon depletion of H3K27me3 via inhibition of the enzymatic subunits of PRC2, EZH1/2. Conversely, primed human embryonic stem cells cannot be driven towards trophectoderm development via PRC2 inhibition. While naïve and primed hESCs share the majority of bivalent promoters, PRC2 contributes to the repression of largely non-overlapping subsets of these promoters in each state, hence H3K27me3-mediated repression provides a highly adaptive mechanism to restrict lineage potential during early human development.

2021-08-23 | GSE181242 | GEO

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