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The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ATAC-seq]

ABSTRACT: The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ATAC-seq]

PROVIDER: PRJNA673866 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12965854_1.fastq.gz	Fastqsanger.gz
	SRR12965854_2.fastq.gz	Fastqsanger.gz
	SRR12965855.fastq.gz	Fastqsanger.gz
	SRR12965856.fastq.gz	Fastqsanger.gz

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The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo

Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo

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The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [HiChIP]

Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [HiChIP]

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The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ChIP-seq]

Project description:The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ChIP-seq]

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The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [HiChIP]

Project description:Transcriptional and phenotypic robustness during development is believed to require complex regulatory landscapes whereby multiple enhancers redundantly control the expression of major cell identity genes. In contrast, we previously described a limited and genetically distinct set of distal regulatory elements, known as poised enhancers (PEs), that control the induction of genes involved in early brain development in a hierarchical and non-redundant manner. Before becoming activated in neural progenitors, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally identified and subsequently characterized using embryonic stem cells (ESC) as in an in vitro differentiation system, it is currently unknown whether PEs are functionally conserved in vivo. Here, we generate and mine various types of genomic data to conclusively show that the epigenetic and 3D structural features of PEs are conserved among pluripotent cells both in vitro and in vivo. Furthermore, by genetically disrupting evolutionary conserved PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential and non-redundant roles during the induction of major anterior neural genes in vivo.

2020-12-31 | GSE160656 | GEO

The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ChIP-seq]

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The chromatin and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo [ATAC-seq]

2020-12-31 | GSE160653 | GEO

The chromatin, topological and regulatory properties of pluripotency-associated poised enhancers are conserved in vivo.

Project description:Poised enhancers (PEs) represent a genetically distinct set of distal regulatory elements that control the expression of major developmental genes. Before becoming activated in differentiating cells, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally characterized in embryonic stem cells (ESC), it is currently unknown whether PEs are functionally conserved in vivo. Here, we show that the chromatin and 3D structural features of PEs are conserved among mouse pluripotent cells both in vitro and in vivo. We also uncovered that the interactions between PEs and their target genes are globally controlled by the combined action of Polycomb, Trithorax and architectural proteins. Moreover, distal regulatory sequences located close to developmental genes and displaying the typical genetic (i.e. CpG islands) and chromatin (i.e. high accessibility and H3K27me3 levels) features of PEs are commonly found across vertebrates. These putative PEs show high sequence conservation within specific vertebrate clades, with only a few being evolutionary conserved across all vertebrates. Lastly, by genetically disrupting PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential roles during the induction of major developmental genes in vivo.

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Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency

Project description:The transition of pluripotent stem cells (PSCs) from primed to naïve states constitutes a prototypical example of cellular plasticity. The naïve state can be stabilized by defined chemical cocktails that block extracellular signals, notably including the MEK pathway. However, little is known regarding the underlying transcriptional mechanisms. Here, we report that the transcriptional landscape of the naïve state can be mimicked in mouse and human PSCs by stimulating transcriptional enhancers. This is attained by inhibiting the CDK8 and CDK19 kinases, which are negative regulators of Mediator, a critical component of enhancer function. Mechanistically, CDK8/19i triggers a global increase in the recruitment of RNA Pol II at promoters and enhancers, hyperactivating enhancers and their target genes. Lastly, the emergence of naïve pluripotency in the pre-implantation epiblast coincides with a marked reduction in CDK8/19 activity, and CDK8/19i blocks its subsequent developmental progression. These findings suggest that naïve pluripotency during development includes hyperactivation of enhancers and can be captured in vitro, either by blunting extracellular signaling, or by stimulating enhancer-driven transcription. These principles may apply to other cellular transitions.

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Histone H3K27ac separates active from poised enhancers and predicts developmental state

Project description:This SuperSeries is composed of the following subset Series: GSE23907: Histone H3K27ac separates active from poised enhancers and predicts developmental state (gene expression data) GSE24164: ChIP-Seq of chromatin marks at distal enhancers in Mouse Embryonic Stem Cells and adult tissues. Refer to individual Series

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

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.

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