Cell type-specific role of CBX2-cPRC1 at the onset of spermatogonial differentiation [CUT&RUN]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA865371 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20755304_1.fastq.gz | Fastqsanger.gz | |||
| SRR20755304_2.fastq.gz | Fastqsanger.gz | |||
| SRR20755305_1.fastq.gz | Fastqsanger.gz | |||
| SRR20755305_2.fastq.gz | Fastqsanger.gz | |||
| SRR20755306_1.fastq.gz | Fastqsanger.gz |
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Project description:Polycomb group (PcG) proteins maintain the repressed state of lineage-inappropriate genes and are therefore essential for embryonic development and adult tissue homeostasis. One critical function of PcG complexes is modulating chromatin structure. Canonical Polycomb repressive complex 1 (cPRC1), particularly its component CBX2, can compact chromatin and phase separate in vitro. These activities are hypothesized to be critical for forming a repressed physical environment in cells. While much has been learned by studying these PcG activities in cell culture models, it is largely unexplored how cPRC1 regulates adult stem cells and their subsequent differentiation during tissue homeostasis in living animals. Here we show that CBX2 is upregulated as spermatogonial stem cells differentiate and is required in the differentiating spermatogonia of the male germ line. CBX2 forms condensates, similar to previously described Polycomb-bodies, that co-localize with target genes that are repressed in differentiating spermatogonia. Single cell analyses of mosaic Cbx2 mutant testes show CBX2 is specifically required to produce differentiating, A1 spermatogonia. Furthermore, the domain of CBX2 responsible for compaction and phase separation is needed for the long-term maintenance of male germ cells in the animal. These results emphasize that the regulation of chromatin structure by CBX2 at a specific stage of spermatogenesis is critical for the continued production of sperm and, ultimately, the transmission of genetic material to the next generation.
2023-08-14 | GSE210367 | GEO
Project description:Polycomb group (PcG) proteins maintain the repressed state of lineage-inappropriate genes and are therefore essential for embryonic development and adult tissue homeostasis. One critical function of PcG complexes is modulating chromatin structure. Canonical Polycomb repressive complex 1 (cPRC1), particularly its component CBX2, can compact chromatin and phase separate in vitro. These activities are hypothesized to be critical for forming a repressed physical environment in cells. While much has been learned by studying these PcG activities in cell culture models, it is largely unexplored how cPRC1 regulates adult stem cells and their subsequent differentiation during tissue homeostasis in living animals. Here we show that CBX2 is upregulated as spermatogonial stem cells differentiate and is required in the differentiating spermatogonia of the male germ line. CBX2 forms condensates, similar to previously described Polycomb-bodies, that co-localize with target genes that are repressed in differentiating spermatogonia. Single cell analyses of mosaic Cbx2 mutant testes show CBX2 is specifically required to produce differentiating, A1 spermatogonia. Furthermore, the domain of CBX2 responsible for compaction and phase separation is needed for the long-term maintenance of male germ cells in the animal. These results emphasize that the regulation of chromatin structure by CBX2 at a specific stage of spermatogenesis is critical for the continued production of sperm and, ultimately, the transmission of genetic material to the next generation.
2023-08-14 | GSE222146 | GEO
Project description:Polycomb group (PcG) proteins maintain the repressed state of lineage-inappropriate genes and are therefore essential for embryonic development and adult tissue homeostasis. One critical function of PcG complexes is modulating chromatin structure. Canonical Polycomb repressive complex 1 (cPRC1), particularly its component CBX2, can compact chromatin and phase separate in vitro. These activities are hypothesized to be critical for forming a repressed physical environment in cells. While much has been learned by studying these PcG activities in cell culture models, it is largely unexplored how cPRC1 regulates adult stem cells and their subsequent differentiation during tissue homeostasis in living animals. Here we show that CBX2 is upregulated as spermatogonial stem cells differentiate and is required in the differentiating spermatogonia of the male germ line. CBX2 forms condensates, similar to previously described Polycomb-bodies, that co-localize with target genes that are repressed in differentiating spermatogonia. Single cell analyses of mosaic Cbx2 mutant testes show CBX2 is specifically required to produce differentiating, A1 spermatogonia. Furthermore, the domain of CBX2 responsible for compaction and phase separation is needed for the long-term maintenance of male germ cells in the animal. These results emphasize that the regulation of chromatin structure by CBX2 at a specific stage of spermatogenesis is critical for the continued production of sperm and, ultimately, the transmission of genetic material to the next generation.
2023-08-14 | GSE210368 | GEO
Project description:Cell type-specific role of CBX2-cPRC1 at the onset of spermatogonial differentiation
| PRJNA865363 | ENA
Project description:Cell type-specific role of CBX2-cPRC1 at the onset of spermatogonial differentiation [scRNA-Seq]
| PRJNA865370 | ENA
Project description:Cell type-specific role of CBX2-cPRC1 at the onset of spermatogonial differentiation [RNA-seq]
| PRJNA918373 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-08-14 | GSE210369 | GEO
Project description:Polycomb group proteins play important roles in developmental and cell proliferation processes. We demonstrate that the PRC1 protein CBX2 is critical for heterochromatin homeostasis, chromosome stability and the prevention of premature cellular senescence. Purpose: Use of Next-generation sequencing (NGS) to assess transcriptional (RNAseq) profiles and changes in chromatin accessibility in WT and Cbx2-/- fibroblasts prior to the onset of premature senescence.
2020-08-20 | GSE156413 | GEO
Project description:Leukemias are characterized by bone marrow failure due to oncogenic mutations of hematopoietic stem cells (HSC) or blood precursor cells. HSC differentiation and self-renewal properties are tightly regulated by Polycomb group (PcG) proteins, a well-characterized family of transcriptional epigenetic regulators. PcG proteins form two canonical complexes: Polycomb repressive complex 1 (PRC1), and Polycomb repressive complex 2 (PRC2).CBX proteins link the activity of PRC1 with PRC2, serving as critical regulators of PcG-mediating activity. While the functional role of some CBX proteins in cancer has been largely explored, recent reports support the specific role of CBX2 in human tumors, thus it represent a promising new target for anti-cancer strategies. To date, chromodomain inhibitors have been identified for CBX7 , but no molecules inhibiting CBX2 have been described. Nevertheless, different chromatin-modulating drugs such as histone deacetylase inhibitors (HDACi) are reported to regulate CBX2 targets on chromatin, suggesting that HDACi might be used to indirectly modulate aberrant effects of CBX2 in cancer. We describe a novel SAHA-mediated mechanism of CBX2 post-translational regulation. We found that CBX2 undergoes SAHA-induced SUMO2/3 modification and that CBX2 SUMOylation promotes its ubiquitination and proteasome-dependent degradation. We also identified the specific molecular pathway and key players regulating CBX2 stability, demonstrating that CBX4 and RNF4 act as the E3 SUMO and E3 ubiquitin ligase, respectively. Additionally, CBX2-depleted leukemic cells display impaired proliferation, showing that CBX2 is required for leukemia cell clonogenicity. Our study provides the first evidence of a non-canonical SAHA-mediated anti-tumorigenic activity via CBX2 SUMOylation and degradation
2018-02-27 | PXD008287 | Pride
Project description:The dynamic epigenome and proteins specialized in the interpretation of epigenetic marks critically contribute to leukemic pathogenesis but also offer opportunities for alternative therapeutic avenues. Targeting novel chromatin readers involved in leukemogenesis may thus provide new anticancer strategies. Accumulating evidence suggests that the PRC1 complex member CBX2 is overexpressed in solid tumors and promotes cancer cell survival. However, its role in leukemia is unclear. We found CBX2 overexpressed in leukemia both in vitro and ex vivo samples compared to CD34+ cells. Decreased CBX2 RNA levels prompted a robust reduction in cell proliferation and induction of apoptosis. Similarly, sensitivity to CBX2 silencing was observed in primary acute myeloid leukemia samples. CBX2 suppression also led to increased genome-wide chromatin accessibility followed by alteration of leukemic cell transcriptional programs, resulting in enrichment of cell death pathways and downregulation of survival genes. Intriguingly, CBX2 silencing induced epigenetic reprogramming at p38 MAPK-associated regulatory sites with consequent deregulation of gene expression. Our results identify CBX2 as a crucial player in leukemia progression and unveil a potential druggable CBX2-p38 MAPK route in AML.
2022-06-11 | GSE193477 | GEO