Loss of PRC1 activity in different stem cell compartments activates a common transcriptional program with cell-type dependent outcome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA483871 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7631550.fastq.gz | Fastqsanger.gz | |||
| SRR7631551.fastq.gz | Fastqsanger.gz | |||
| SRR7631546.fastq.gz | Fastqsanger.gz | |||
| SRR7631547.fastq.gz | Fastqsanger.gz | |||
| SRR7631548.fastq.gz | Fastqsanger.gz |
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Project description:Polycomb Repressive Complexes (PRCs) are evolutionary-conserved multiprotein complexes that maintain transcriptional repression during development and differentiation to establish and preserve cell identity. Through the enzymatic activity of the subunits Ring1A and Ring1B, PRC1 monoubiquitinates histone H2A on lysine 119, promoting nucleosome compaction. We recently described a fundamental role of PRC1 in preserving intestinal stem cells identity through the inhibition of non-lineage specific transcription factors. To gain more insight into the role of PRC1 in adult stem cell maintenance, we have now investigated its role in LGR5+ hair follicle stem cells during physiological regeneration. We show that PRC1 depletion in LGR5+ cells severely affects hair regeneration. Differently from what we described for ISCs, the release of target transcriptional repression upon loss of PRC1 activity induces the ectopic activation of an epidermal-specific program. Our data support a general role of PRC1 in preserving cell identity that is shared between different stem cell compartments. However, we propose that the final outcome of the ectopic activation of non-lineage specific transcription factors observed upon loss of PRC1 in stem cells is largely context-dependent and likely related to the transcription factors repertoire and the specific epigenetic landscape of the different cellular compartments.
2019-06-20 | GSE117967 | GEO
Project description:Polycomb repressive complexes are evolutionarily conserved complexes that maintain transcriptional repression during development and differentiation to establish and preserve cell identity. We recently described the fundamental role of PRC1 in preserving intestinal stem cell identity through the inhibition of non-lineage-specific transcription factors. To further elucidate the role of PRC1 in adult stem cell maintenance, we now investigated its role in LGR5+ hair follicle stem cells during regeneration. We show that PRC1 depletion severely affects hair regeneration and, different from intestinal stem cells, derepression of its targets induces the ectopic activation of an epidermal-specific program. Our data support a general role of PRC1 in preserving stem cell identity that is shared between different compartments. However, the final outcome of the ectopic activation of non-lineage-specific transcription factors observed upon loss of PRC1 is largely context-dependent and likely related to the transcription factors repertoire and specific epigenetic landscape of different cellular compartments.
| S-EPMC6520019 | biostudies-literature
Project description:Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. mRNA profiles of P1 brain from wild type mice were generated by deep sequencing
2014-12-18 | E-GEOD-60410 | biostudies-arrayexpress
Project description:Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. ChIP-seq experiments of PRC1 components, PolII as well as histone modifications were performed either in mouse whole brain or in human 293T-REx lines expressing FLAG/HA-tagged subunits. RNA-seq was performed to analyze the expression profile of mouse whole brain.
2014-12-18 | E-GEOD-60409 | biostudies-arrayexpress
Project description:Polycomb repressive complexes 1 and 2 (PRC1 and 2) repress lineage inappropriate genes during development to maintain proper cellular identities. To reveal the function of a variant PRC1 containing PCGF1 (PCGF1-PRC1), we prepared PCGF1 interacting proteins by immunoprecipitation and characterized them by LC-MS/MS.
2022-11-30 | PXD036330 | Pride
Project description:Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.
2014-12-18 | GSE60410 | GEO
Project description:Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrate that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity and AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq of AUTS2 shows that it regulates neuronal gene expression through promoter association. Conditional CNS targeting of Auts2 in a mouse model leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.
2014-12-18 | GSE60409 | GEO
Project description:This work study the effects of PRC1 phosphorylation by CDK1 and PLK1.
2024-11-01 | PXD055933 | Pride
Project description:Protein regulator of cytokinesis 1 (PRC1) is a microtubule-bundling protein with essential roles in mitosis and cytokinesis. In this study we investigated the potential nuclear functions of PRC1 and the consequences of overexpression of PRC1 by using lung cancer cell lines stably expressing inducible expression constructs for PRC1. Ectopically expressed PRC1 resulted in proliferation defects, multi-nucleation and enlargement of cells which were directly linked to microtubule-bundling within the cytoplasm. Genome wide expression profiling by RNA sequencing revealed that the p53 pathway is activated upon overexpression of PRC1 resulting in cellular senescence. A mutant of PRC1 unable to enter into the nucleus induced the same gene sets as wildtype PRC1, suggesting that PRC1 has no nuclear-specific functions in lung cancer cells. The depletion of p53 switched the response to PRC1 overexpression or depletion from senescence to apoptosis. In addition, treatment with cisplatin, a commonly used chemotherapeutic drug, enhanced the proliferation defects due to deregulated PRC1, implicating PRC1 as a possible therapeutic target for cancer. Taken together, PRC1 needs to be tightly regulated to allow unperturbed proliferation of lung cancer cells.
2021-09-01 | GSE137940 | GEO
Project description:Polycomb group proteins form two main complexes, PRC2 and PRC1, which generally coregulate their target genes. Here, we show that PRC1 components act as neoplastic tumor suppressors independently of PRC2 function. By mapping the distribution of PRC1 components and the histone H3K27me3 mark, we identify genes that acquire PRC1 and H3K27me3 in larvae, and a much larger set of genes bound by PRC1 in the absence of H3K27me3 in larval tissues. These genes massively outnumber canonical targets and they are preeminently involved in the regulation of cell proliferation, signaling and polarity. Mutation in PRC1 components specifically deregulates this set of genes, whereas canonical targets are derepressed in both PRC1 and PRC2 mutants. In human ES cells, PRC1 components colocalize with H3K27me3 like in Drosophila embryos, whereas they are selectively recruited to a large set of proliferation and signaling-associated genes in differentiated cell types, showing that the redeployment of PRC1 components during development is evolutionarily conserved. Comparative study of Polycomb group proteins and histon marks during development with ChIP-Seq and RNA-Seq data in eye discs and wing discs (L3 stage) in Drosophila
2016-07-18 | E-GEOD-74080 | biostudies-arrayexpress