RNA-seq analyses of wild-type and PML KO mESCs
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE135557 | 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, 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: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:TRIM33 is a chromatin reader required for mesendoderm differentiation upon activation of Nodal signaling. But, its role in mESCs is still elusive. Here, we found that TRIM33 co-localizes with promyelocytic leukemia nuclear bodies (PML NBs) specifically in mESCs to mediate Nodal signaling-directed transcription of Lefty1/2. We showed that TRIM33 puncta formation in mESCs depends on PML and specific assembly of PML NBs. Moreover, TRIM33 and PML co-regulate Lefty1/2 expression in mESCs. In addition, both PML and mESCs-specific PML NBs are required for TRIM33 recruitment at Lefty1/2 loci. Remarkably, PML NBs directly associate with the Lefty1/2 loci in mESCs. Finally, a TurboID proximity labeling experiment confirmed that TRIM33 is highly enriched in the mESCs-specific PML NBs. Thus, our study provides the mechanistic insight about TRIM33 condensate in regulating Nodal signaling-directed transcription in mESCs, it also reveals that PML NBs recruit distinct sets of client proteins in cell context dependent manner.
2022-12-08 | GSE199738 | GEO
Project description:PML drives the assembly of PML Nuclear Bodies (NBs), where it recruits many serendipitously-identified proteins, including the SUMO-E2 enzyme UBC9. Interferons, arsenic or oxidative stress, all enhance NB-formation. Here demonstrate that PML is required for efficient basal sumoylation in mouse embryonic stem cells (mESCs) and immediate stress-responsive sumoylation in mouse liver or Acute Promyelocytic Leukemia (APL). Biochemically, PML NBs confer an oxidation-protective environment for the redox-sensitive UBC9 activity, which, together with enzyme/target concentration/immobilization, favors processive SUMO2/3 conjugation. Accordingly, PML-facilitated sumoylation is accompanied by ubiquitination and degradation of some targets. In vivo proteomic analysis of SUMO2 conjugates in APL identified therapy-responsive targets, among which the prominent KAP1 complex of epigenetic regulators. In mESCs, PML is required for SUMO-dependent KAP1 repressive activity and for the resulting silencing of transposable elements and 2-cell-like genes. The ES status is further regulated by a PML-facilitated repressive sumoylation of the Dppa2 zygote genome activation driver. These findings establish the biochemical function of PML NBs in vivo and unveiling an unsuspected epigenetic control of key ESC targets by PML.
2022-09-14 | PXD019609 | Pride
Project description:Heterochromatin is a pivotal element in the functional organization of genomes. In our study, we delve into the heterochromatin pattern of association by the PML (promyelocytic leukemia) protein. By using PML chromatin immunoprecipitation and sequencing data and comparing computational methodologies to depict PML chromatin association, we describe PML-associated domains or PADs as large heterochromatic regions that exhibit similar genomic features across cancer cell lines. We show that PADs are specifically enriched in non-coding genes, duplicated gene clusters, and repetitive DNA elements. Moreover, we find enriched binding motifs of KZFPs, which are involved in orchestrating epigenetic repression at repetitive DNA elements. Hence, our findings suggest that PML conservatively associates to heterochromatic domains enriched in repetitive DNA elements and duplicated gene clusters in cancer. These findings contribute to a broader understanding of the complex regulatory framework of genome organization by heterochromatin in cancer.
2024-08-22 | GSE261929 | GEO
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