Profiling of PML-body associated regions
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE135560 | GEO | 2019/08/14
REPOSITORIES: GEO
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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. 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 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, 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
Project description:Profiling of PML-body associated regions
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Project description:Dissecting roles of PML bodies by genome-wide profiling of PML body-associated regions
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Project description:The transcription factor NF-κB is considered the master regulator of the immune response but also acts broadly to regulate gene expression that influences cell survival, proliferation and differentiation. Post-translational modification of NF-κB, phosphorylation in particular, is essential for the transactivation activity of NF-κB. Emerging evidence suggests that the regulation of NF-κB in the nucleus is critical in controlling gene expression. Promyelocytic Leukemia (PML) is a nuclear protein that forms nuclear bodies (PML NBs), sub-nuclear structures that are associated with transcriptionally active genomic regions that have been implicated in multiple processes such as apoptosis, senescence and anti-viral responses. Chromosomal translocations leading to the expression of a PML-retinoic acid receptor-α (PML-RARα) fusion protein are causative for acute promyelocytic leukemia (APL) characterised by a differentiation block at the promyelocytic state of myeloid development. Here we demonstrate that PML is required for phosphorylation of NF-κB p65 and that PML is essential for NF-κB- induced transcriptional responses. Our analysis of available transcriptional profiles of all-trans retinoic acid treated acute promyelocytic leukemia (APL) cells identifies a NF-κB transcriptional programme suppressed by PML-RARα. We further demonstrate that PML-RARα inhibits NF-κB phosphorylation and transcriptional activity. Our findings demonstrate a critical role for PML in promoting NF-κB transcriptional activity which may contribute to APL initiation and maintenance. WT and PML-/- MEFs were analysed for gene expression analysis. Total of 12 samples, inlcluding triplicates were utilized. WT MEFs and PML-/- were stimulated with TNFα for three hours and analysed for gene expresison using unstimulated WT MEFs as control.
2016-06-01 | E-GEOD-47828 | biostudies-arrayexpress
Project description:A global view of PML-RAR? transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. Complete Abstract: The translocation t(15;17) generates the chimeric PML-RAR? transcription factor that is the initiating event of acute promyelocytic leukemia. A global view of PML-RAR? transcriptional functions was obtained by genome-wide binding and chromatin modification analyses, combined with genome wide expression data. ChIP-chip experiments identified 372 direct genomic PML-RAR? targets. A subset of these was confirmed in primary acute promyelocytic leukemia. Direct PML-RARá targets include regulators of global transcriptional programs as well as critical regulatory genes for basic cellular functions such as cell cycle control and apoptosis. PML-RAR? binding universally led to HDAC1 recruitment, loss of histone H3 acetylation, increased tri-methylation of histone H3 lysine 9 and unexpectedly increased tri-methylation of histone H3 lysine 4. The binding of PMLRAR? to target promoters and the resulting histone modifications resulted in mRNA repression of functionally relevant genes. Taken together our results reveal that the transcription factor PML-RAR? regulates key cancer related genes and pathways by inducing a repressed chromatin formation on its direct genomic target genes. Keywords: ChIP on Chip U937 transfected with an inducible PML-RAR?/empty vecor were induced, harvested and Chromatin-Ips for PML, AcH3 followed by microarray hybridasation were carried out. For detailed procedures see Hoemme et al. "Chromatin modifications induced by PML-RARalpha repress critical targets in leukemogenesis as analyzed by ChIP-Chip"
2008-09-06 | E-GEOD-12641 | biostudies-arrayexpress
Project description:Promyelocytic Leukemia Nuclear Bodies (PML NBs) are nuclear membrane-less organelles physically associated with chromatin underscoring their crucial role in genome function. The H3.3 histone chaperone complex HIRA accumulates in PML NBs upon senescence, viral infection or IFN-I treatment in primary cells. Yet, the molecular mechanisms of this partitioning and its function in regulating histone dynamics have remained elusive. Here, by using specific siRNAs and protein Affimers, we identify intermolecular SUMO-SIM interactions as an essential mechanism for HIRA recruitment in PML NBs. In addition, we demonstrate that HIRA localization in the nuclear bodies is intimately linked to the presence of a soluble pool of H3.3-H4 dimers inside PML NBs, that is not found in cancer cells. Transcription inhibition prevents HIRA accumulation in PML NBs underscoring the importance of transcriptional activity to drive HIRA through PML NBs. Finally, in the context of inflammatory responses, HIRA and PML are necessary for the prolonged H3.3 deposition at the transcriptional end sites of interferon-stimulated genes (ISGs), well beyond the peak of transcription. We thus propose that HIRA partitioning in PML NBs is essential to regulate H3.3 deposition on transcriptionally active regions.
2023-05-30 | GSE186937 | GEO
Project description:Promyelocytic Leukemia Nuclear Bodies (PML NBs) are nuclear membrane-less organelles physically associated with chromatin underscoring their crucial role in genome function. The H3.3 histone chaperone complex HIRA accumulates in PML NBs upon senescence, viral infection or IFN-I treatment in primary cells. Yet, the molecular mechanisms of this partitioning and its function in regulating histone dynamics have remained elusive. Here, by using specific siRNAs and protein Affimers, we identify intermolecular SUMO-SIM interactions as an essential mechanism for HIRA recruitment in PML NBs. In addition, we demonstrate that HIRA localization in the nuclear bodies is intimately linked to the presence of a soluble pool of H3.3-H4 dimers inside PML NBs, that is not found in cancer cells. Transcription inhibition prevents HIRA accumulation in PML NBs underscoring the importance of transcriptional activity to drive HIRA through PML NBs. Finally, in the context of inflammatory responses, HIRA and PML are necessary for the prolonged H3.3 deposition at the transcriptional end sites of interferon-stimulated genes (ISGs), well beyond the peak of transcription. We thus propose that HIRA partitioning in PML NBs is essential to regulate H3.3 deposition on transcriptionally active regions.
2023-05-25 | GSE233298 | GEO
Project description:The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors and transcriptional regulators converge to be regulated. Specific associations of PML and PML-NBs with chromatin are described in different cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in a cellular context where it regulates relevant phenotypes is still lacking.We examined the role of PML in chromatin association and transcription in triple-negative breast cancer (TNBC), a pathological condition where PML exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a cell type-relevant function of transcriptional regulation. PML also plays an indirect regulatory function in TBNC cells by promoting the expression of pro-metastatic genes outside PADs.Our findings demonstrate that PML is an important transcriptional regulator of metastasis and pro-oncogenic metagenes in TNBC cells, via distinct molecular activities that include indirect transcriptional regulation and direct epigenetic organization of heterochromatin domains that embed regions of localized transcriptional activity.
2023-09-11 | GSE240309 | GEO