CBX8-PRC1 regulates adult olfactory neurogenesis and epithelial homeostasis
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ABSTRACT:
PROVIDER: PRJNA512013 | ENA |
REPOSITORIES: ENA
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Project description:The polycomb group protein, CBX8, is a neuron-specific component of Polycomb repressive complex 1 (PRC1) in the adult olfactory epithelium. We performed loss of function assays in an in vitro model of the regeneratng olfactory epithelium to determine the role of CBX8 in adult olfactory neurogenesis. Whole-transcriptome analysis highlighted the importance of CBX8-PRC1 in the regulation of adult neurogenesis in the olfactory epithelium.
2020-12-25 | GSE124441 | GEO
Project description:The polycomb group protein, CBX8, is a neuron-specific component of Polycomb repressive complex 1 (PRC1) in the adult olfactory epithelium. We performed ChIP-seq to identify genes occupied by CBX8-PRC1.
2020-12-25 | GSE124440 | GEO
Project description:Canonical targeting of Polycomb Repressive Complex 1 (PRC1) to repress developmental genes is mediated by cell type-specific, paralogous chromobox (CBX) proteins (CBX2, 4, 6, 7 and 8). Based on their central role in silencing and their dysregulation associated with human disease including cancer, CBX proteins are attractive targets for small molecule chemical probe development. Here, we have used a quantitative and target-specific cellular assay to discover a potent positive allosteric modulator (PAM) of CBX8. The PAM activity of UNC7040 antagonizes H3K27me3 binding by CBX8 while increasing interactions with nucleic acids. We show that treatment with UNC7040 leads to efficient and selective eviction of CBX8-containing PRC1 from chromatin, loss of silencing and reduced proliferation across different cancer cell lines. Our discovery and characterization of UNC7040 not only reveals the most cellularly potent CBX8-specific chemical probe to date, but also corroborates a mechanism of Polycomb regulation by non-specific CBX nucleotide binding activity.
2022-01-03 | GSE182592 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-12-25 | GSE124442 | GEO
Project description:REPROGRAMMING CBX8-PRC1 FUNCTION WITH A POSITIVE ALLOSTERIC MODULATOR
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Project description:We performed single-cell RNAseq of human olfactory and respiratory epithelium and found evidence of olfactory neurogenesis and differentiation in adult humans.
2019-12-18 | GSE139522 | GEO
Project description:Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Here, we show that several differentiation genes transiently recruit a Cbx8-containing Polycomb repressive complex (PRC) 1 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. This correlates with a reduction in low but detectable levels of histone H3 lysine 27 acetylation. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3. The composition of PRC1 is highly modular and changes when ES cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs. Examination of cbx8 in ES E14 mouse cells in 2 condition before and after 72h stimulation with retinoic acid compared with IgG
2014-11-04 | E-GEOD-54052 | biostudies-arrayexpress
Project description:Parkinson’s disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the olfactory pathway of transgenic (Tg) mice of both sexes expressing the human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6–7 and 12–14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons (PNs) of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at six to seven months and OB periglomerular cells at 12–14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endocytic and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12–14 months. Our data suggest that (1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; (2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; (3) α-syn pathology is restricted to projection neurons in the olfactory pathway; (4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and (5) synaptic endocytosis and exocytosis defects in the OB may further explain olfactory deficits.
2023-01-13 | PXD039396 | Pride
Project description:Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Here, we show that several differentiation genes transiently recruit a Cbx8-containing Polycomb repressive complex (PRC) 1 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. This correlates with a reduction in low but detectable levels of histone H3 lysine 27 acetylation. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3. The composition of PRC1 is highly modular and changes when ES cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.
2014-11-04 | GSE54052 | GEO
Project description:Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Here, we show that several differentiation genes transiently recruit a Cbx8-containing Polycomb repressive complex (PRC) 1 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. This correlates with a reduction in low but detectable levels of histone H3 lysine 27 acetylation. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3. The composition of PRC1 is highly modular and changes when ES cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.
2014-11-04 | GSE54051 | GEO