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A functional link between nuclear RNA decay and transcritional control mediated by the Polycomb Repressive Complex 2

ABSTRACT: A functional link between nuclear RNA decay and transcritional control mediated by the Polycomb Repressive Complex 2

PROVIDER: PRJNA565723 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10123900.fastq.gz	Fastqsanger.gz
	SRR10123901.fastq.gz	Fastqsanger.gz
	SRR10123902.fastq.gz	Fastqsanger.gz
	SRR10123903.fastq.gz	Fastqsanger.gz
	SRR10123904.fastq.gz	Fastqsanger.gz

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A functional link between nuclear RNA decay and transcritional control mediated by the Polycomb Repressive Complex 2

Project description:Pluripotent embryonic stem (ES) cells constitute an essential cellular niche in animal development. It is well documented that ES cells are sustained by epigenetic and transcriptional regulation, but the role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the ‘polyA RNA exosome targeting’ (PAXT) connection, and transcriptional control, regulated by the Polycomb Repressive Complex 2 (PRC2). Knockout of the PAXT component ZFC3H1 in mouse ES cells impairs their differentiation. In addition to the upregulation of bona fide PAXT substrates, Zfc3h1-/- cells abnormally express developmental genes usually subjected to PRC2-mediated repression. Such de-repression is paralleled by decreased PRC2 binding to chromatin at target genes, and low PRC2-directed H3K27 methylation. PRC2 complex stability is compromised in Zfc3h1-/- cells with elevated levels of unspecific RNA bound to PRC2 components. We propose that excess RNA hampers PRC2 function through its sequestration from DNA and complex destabilisation. Our results highlight the importance of balancing nuclear RNA levels and demonstrate the capacity of bulk RNA to regulate chromatin-associated proteins.

2019-11-12 | GSE137491 | GEO

A Functional Link between Nuclear RNA Decay and Transcriptional Control Mediated by the Polycomb Repressive Complex 2.

Project description:Pluripotent embryonic stem cells (ESCs) constitute an essential cellular niche sustained by epigenomic and transcriptional regulation. Any role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the poly(A) RNA exosome targeting (PAXT) connection, and transcriptional control by the polycomb repressive complex 2 (PRC2). Knockout of the PAXT component ZFC3H1 impairs mouse ESC differentiation. In addition to the upregulation of bona fide PAXT substrates, Zfc3h1-/- cells abnormally express developmental genes usually repressed by PRC2. Such de-repression is paralleled by decreased PRC2 binding to chromatin and low PRC2-directed H3K27 methylation. PRC2 complex stability is compromised in Zfc3h1-/- cells with elevated levels of unspecific RNA bound to PRC2 components. We propose that excess RNA hampers PRC2 function through its sequestration from DNA. Our results highlight the importance of balancing nuclear RNA levels and demonstrate the capacity of bulk RNA to regulate chromatin-associated proteins.

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E2f6 and Mga transcription factors link polycomb repressive complex PRC1.6 to methylation of CpG islands

Project description:E2f6 and Mga transcription factors link polycomb repressive complex PRC1.6 to methylation of CpG islands

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Direct Recruitment of Polycomb Repressive Complex 1 (PRC1) to Chromatin by Core Binding Transcription Factors

Project description:This SuperSeries is composed of the following subset Series: GSE33653: Direct Recruitment of Polycomb Repressive Complex 1 (PRC1) to Chromatin by Core Binding Transcription Factors (ChIP-Seq) GSE33659: Direct Recruitment of Polycomb Repressive Complex 1 (PRC1) to Chromatin by Core Binding Transcription Factors (microarray) Refer to individual Series

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Loss of Cohesin regulator PDS5A reveals repressive role of Polycomb loops

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Project description:Polycomb proteins assemble to form complexes with important roles in epigenetic regulation. The Polycomb Repressive Complex 2 (PRC2) modulates the di- and tri-methylation of lysine 27 on histone H3, each of which are associated with gene repression. Although three subunits, EZH1/2, SUZ12 and EED, form the catalytic core of PRC2, a wider group of proteins associate with low stoichiometry. This raises the question of whether dynamic variation of the PRC2 interactome results in alternative forms of the complex during differentiation. Here we compared the physical interactions of PRC2 in undifferentiated and differentiated states of NTERA2 pluripotent embryonic carcinoma cells. Label-free quantitative proteomics was used to assess endogenous immunoprecipitation of the EZH2 and SUZ12 subunits of PRC2. A high stringency dataset reflecting the endogenous state of PRC2 was produced that included all previously reported ‘core’ and ‘associated’ PRC2 components, and several novel interacting proteins. Comparison of the interactomes obtained in undifferentiated and differentiated cells revealed candidate proteins that favoured either one or other state. For example, SALL4 and ZNF281 associate with PRC2 in pluripotent cells, while PCL1 and SMAD3 more associate with PRC2 in differentiating cells. Analysis of the mRNA and protein levels of these factors found that their association with PRC2 correlated with their cell state-specific expression. Taken together, we propose that dynamic changes to the PRC2 interactome during differentiation may contribute to directing its activity during cell fate transitions.

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Project description:Polycomb Group (PcG) proteins regulate gene expression through changes to chromatin structure and are essential for development. PcG proteins function together with the Trithorax Group (TrxG) proteins, which affect diverse steps in transcription activation. The PcG and TrxG are genetically and functionally antagonistic, and current understanding suggests a balance of their activities can maintain a wide range of transcription states. PcG and TrxG proteins assemble into a series of complexes. How these complexes work together, how PcG complexes are recruited to target genes, and whether other proteins are involved in their regulation of gene expression remain open questions. We carried out tandem affinity purification followed by mass spectrometry (TAP-MS) on two core components of Drosophila Polycomb Repressive Complex 1 (PRC1). Our data reveal a network of interactions among PcG complexes, and extensive co-purification of TrxG complexes with PRC1. We co-purified >50 transcription factors with PRC1 that were not previously linked to the PcG. Finally, we identify novel co-purifying complexes, including HP1c and PCNA handling complexes. Our resource of candidate PRC1 interacting proteins generate new hypotheses for PRC1 function.

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