Dissecting roles of PML bodies by genome-wide profiling of PML body-associated regions
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ABSTRACT:
PROVIDER: PRJNA559285 | ENA |
REPOSITORIES: ENA
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Project description:The promyelocytic leukemia (PML) body is a phase-separated nuclear structure composed of various proteins including several chromatin regulators, and physically associates with chromatin. To address functional roles of the PML-chromatin association, we conducted genome-wide profiling of PML body-associated regions.
2019-08-14 | GSE135560 | GEO
Project description:Profiling of PML-body associated regions
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Project description:Identifying the functions of proteins, which define specific subnuclear structures and territories, is important for understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML bodies and co-localizes with the proto-oncogenic protein PML and Daxx, proteins with critical roles in oncogenic transformation, interferon-mediated viral resistance and response to PML-directed cancer therapeutics. Sp100 isoforms contain PHD, Bromo and HMG domains and are highly sumoylated at ND10/PML bodies, all characteristics suggestive of a role in chromatin mediated gene regulation. However, no clear role for the Sp100 component of PML bodies in oncogenesis has been defined. Using isoform-specific knockdown techniques, we show that most human diploid fibroblasts, which lack Sp100, rapidly senesce and discuss gene expression changes associated with this rapid senescence.
2012-12-04 | GSE20613 | GEO
Project description:The Sp100 component of ND10/PML bodies is a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Identifying the functions of proteins, which define specific subnuclear structures and territories, is important for understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML bodies and colocalizes with the proto-oncogenic protein PML and Daxx, proteins with critical roles in oncogenic transformation, interferon-mediated viral resistance and response to PML-directed cancer therapeutics. Sp100 isoforms contain PHD, Bromo and HMG domains and are highly sumoylated at ND10/PML bodies, all characteristics suggestive of a role in chromatin mediated gene regulation. However, a clear role for Sp100 in oncogenesis has not been defined. Using isoform-specific knockdown techniques, we show that most human diploid fibroblasts, which lack Sp100, rapidly senesce. microarray analysis of mRNAs expression in BJV (collected at passage 47) and BJ-S (collected at passage 35). In addition, samples were treated for 24 h with 1000 U/ml IFNB. All RNAs were collected in triplicates of biological samples.
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Project description:Point mutations in histone variant H3.3 (H3.3 K27M, H3.3 G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in paediatric gliomas. It is clear that H3.3 point mutations affect many chromatin modifications but the exact oncogenic mechanisms are an area of active investigation. Histone H3.3 has been previously linked to PML, a gene which is frequently mutated in Acute Promyelocytic Leukaemia. We find that H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to PML-mutated Acute Promyelocytic Leukaemias, H3.3-mutated patient-derived gliomas cells are also sensitive to drugs which target PML bodies. We identify PML as a contributor to oncogenesis in H3.3-mutated gliomas and our results indicate that PML-targeting strategies may prove effective at treating H3.3-mutated paediatric gliomas.
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Project description:A proteomic analysis of PML bodies purified from U2OS cells expressing YFP-PMLV either treated or not with 1uM arsenic for 2 hours, in comparison with parallel purifications from wt-U2OS cells treated identically.
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Project description:Promyelocytic leukemia (PML) body is a phase-separated nuclear structure composed of various proteins including several chromatin regulators, and physically associates with chromatin, implying its crucial roles for particular genome functions. To investigate functional roles of PML bodies in chromatin organization, we conducted ATAC-seq with wild-type and PML KO mESCs.
2019-08-14 | GSE135561 | GEO
Project description:Promyelocytic leukemia (PML) body is a phase-separated nuclear structure composed of various proteins including several chromatin regulators, and physically associates with chromatin. To address roles of PML bodies in transcriptional regulation, we performed RNA-seq analyses with wild-type and PMK knockout mESCs
2019-08-14 | GSE135557 | GEO
Project description:Promyelocytic leukemia (PML) body is a phase-separated nuclear structure composed of various proteins including several chromatin regulators, and physically associates with chromatin, implying its crucial roles for particular genome functions. To investigate roles of PML bodies in transcriptional regulation, we conducted ChIP-seq analysis for histone modifications, including H3K4me3, H3K27ac, H3K27me3, and H3K9ac with wild-type and PML knockout mESCs.
2019-08-14 | GSE135562 | GEO