Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1165040.fastq.gz | Fastqsanger.gz | |||
| SRR1165050.fastq.gz | Fastqsanger.gz | |||
| SRR1165041.fastq.gz | Fastqsanger.gz | |||
| SRR1165051.fastq.gz | Fastqsanger.gz | |||
| SRR1165042.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:We analyzed the genome wide localization of H3K4me3, H3K27me3 and the NUP98-PHF23 (with V5 tag) fusion protein which binds H3K4me3 via its PHD finger, using ChIP-seq. Results correlated with gene expression profiles. NUP98-PHF23 bound only 1.6% of H3K4me3 marks including Hoxa/b + Meis1. Assess H3K4me3 and H3K27me3 histone marks, and correlate these marks with chromatin binding of the NP23 fusion protein using lymphoblast and myeloblast cell lines derived from NP23 leukemias.
2014-03-06 | E-GEOD-54786 | biostudies-arrayexpress
Project description:We analyzed the genome wide localization of H3K4me3, H3K27me3 and the NUP98-PHF23 (with V5 tag) fusion protein which binds H3K4me3 via its PHD finger, using ChIP-seq. Results correlated with gene expression profiles. NUP98-PHF23 bound only 1.6% of H3K4me3 marks including Hoxa/b + Meis1.
2014-03-06 | GSE54786 | GEO
Project description:Recurrent cancer-causing fusions of NUP98 produce higher-order assemblies known as condensates. How NUP98 oncofusion-driven condensates activate oncogenes remains poorly understood. Here, we investigate NUP98-PHF23, a leukemogenic chimera of the disordered FG-repeats-rich region of NUP98 and the H3K4me3/2-binding PHD finger domain of PHF23. Our integrated analyses using mutagenesis, proteomics, genomics, and condensate reconstitution demonstrate that the PHD domain targets condensates to H3K4me3/2-demarcated developmental genes while the FG repeats determine condensate composition and gene activation. The FG repeats are necessary to form condensates that partition a specific set of transcriptional regulators, notably the KMT2/MLL family of H3K4 methyltransferases, histone acetyltransferases and BRD4. The FG repeats are sufficient to partition these transcriptional regulators and activate a reporter when tethered to a locus. NUP98-PHF23 assembles the chromatin-bound condensates that partition multiple positive regulators, initiating a feed-forward loop of reading-and-writing active histone modifications. This network of interactions enforces an open chromatin landscape at proto-oncogenes, thereby driving cancerous transcriptional programs.
2024-12-31 | PXD056948 | Pride
Project description:Cancer-associated genetic aberrations, such as the nucleoporin 98 (NUP98) gene rearrangement detected in human leukemias, often produce condensates, a type of membrane-less biomolecular assemblies. How exactly the cancer-related condensation contributes to oncogenesis remains far from clear. Here, we investigate NUP98-PHF23, a leukemia-causing chimeric protein that fuses NUP98’s sequence enriched in phenylalanine-and-glycine repeats (FG repeats, also known as intrinsically disordered region [IDR]) in-frame with PHF23’s PHD finger, a domain that specifically ‘reads’ and binds H3K4 trimethylation (H3K4me3). Our integrated analyses using protein module mutagenesis, cell imaging, genomic profiling and condensation reconstitution collectively demonstrate a multifaced role for NUP98’s FG repeats in driving fusion condensation while recruiting and co-mixing with a set of histone modifiers and chromatin remodelers, notably the MLL family of H3K4 methylation-‘writing’ enzymes. The H3K4me3-‘reading’ PHD finger and NUP98’s IDR are cooperative in mediating efficient targeting of NUP98-PHF23 and its coactivators onto leukemic genes, leading to active transcription. Together, we show that NUP98-PHF23 coordinates a set of homotypic and heterotypic interactions (IDR:IDR, IDR:coactivator and PHD:histone) to organize formation of the chromatin-bound multi-component condensates, wherein a feedforward loop involving the ‘reading’ and ‘writing’ of H3K4 methylation acts to enforce an open chromatin landscape at leukemogenic loci, thereby driving oncogenic transformation.
2025-01-30 | GSE255508 | GEO
Project description:Recurrent cancer-causing fusions of NUP98 produce higher-order assemblies known as condensates. How NUP98 oncofusion-driven condensates activate oncogenes remainspoorly understood. Here, we investigate NUP98-PHF23, a leukemogenic chimera of the FG-repeat region of NUP98 and the H3K4me3-binding PHD finger of PHF23. Our integrated analyses using mutagenesis, proteomics, genomics, and condensate reconstitution demonstrate that the PHD finger targets condensates to H3K4me3-demarcated developmental genes and the FG repeats determine condensate composition and gene activation. The FG repeats are necessary to form condensates that partition a specific set of transcriptional regulators, notably the MLL family of H3K4 methylation-writing enzymes and BRD4. The FG repeats are sufficient, when tethered to the genome, to partition these transcriptional regulators and activate genes. NUP98-PHF23 assembles chromatin-bound condensates that partition multiple positive regulators, initiating a feed-forward loop of reading-and-writing active histone modifications. This network of interactions enforces an open chromatin landscape at proto-oncogenes, thereby driving cancerous transcriptional programs.
2025-01-30 | GSE280397 | GEO
Project description:The dysregulation of plant homeodomain (PHD) fingers has been implicated in several human diseases, including cancer. In a subset of aggressive acute myeloid leukemia (AML), chromosomal translocations that involve nucleoporin 98 (NUP98), a component of the nuclear pore complex, and a PHD finger-containing protein, such as KDM5A/JARID1A, PHF23 and BPTF, generate potent oncoproteins (namely NUP98-KDM5A, NUP98-PHF23 and NUP98-BPTF; or together termed as NUP98-PHD fusions) that are able to arrest hematopoietic differentiation and induce acute myeloid leukemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukemic transformation. An overlap of NUP98-KDM5A oncoprotein binding sites and H3K4me3-positive loci at the Hoxa/b gene clusters and Meis1 in ChIP-seq together with NMR analysis of the H3K4me3-binding sites of the PHD fingers from PHF23, KDM5A and BPTF suggests a common PHD finger-dependent mechanism that promotes leukemogenesis by this type of NUP98-PHD finger fusions. Disulfiram (DS), a small molecule compound that directly targets the PHD finger, shows anti-proliferation effects in AML cells expressing NUP98-PHD through the conserved inhibitory mechanism. Our findings highlight the direct correlation between the abilities of NUP98-PHD finger fusion chimeras to associate with H3K4me3-enriched chromatin and leukemic transformation.
2020-07-13 | GSE146693 | GEO
Project description:Cancer-associated genetic aberrations, such as the nucleoporin 98 (NUP98) gene rearrangement detected in human leukemias, often produce condensates, a type of membrane-less biomolecular assemblies. How exactly the cancer-related condensation contributes to oncogenesis remains far from clear. Here, we investigate NUP98-PHF23, a leukemia-causing chimeric protein that fuses NUP98’s sequence enriched in phenylalanine-and-glycine repeats (FG repeats, also known as intrinsically disordered region [IDR]) in-frame with PHF23’s PHD finger, a domain that specifically ‘reads’ and binds H3K4 trimethylation (H3K4me3). Our integrated analyses using protein module mutagenesis, cell imaging, genomic profiling and condensation reconstitution collectively demonstrate a multifaced role for NUP98’s FG repeats in driving fusion condensation while recruiting and co-mixing with a set of histone modifiers and chromatin remodelers, notably the MLL family of H3K4 methylation-‘writing’ enzymes. The H3K4me3-‘reading’ PHD finger and NUP98’s IDR are cooperative in mediating efficient targeting of NUP98-PHF23 and its coactivators onto leukemic genes, leading to active transcription. Together, we show that NUP98-PHF23 coordinates a set of homotypic and heterotypic interactions (IDR:IDR, IDR:coactivator and PHD:histone) to organize formation of the chromatin-bound multi-component condensates, wherein a feedforward loop involving the ‘reading’ and ‘writing’ of H3K4 methylation acts to enforce an open chromatin landscape at leukemogenic loci, thereby driving oncogenic transformation.
2025-01-30 | GSE255868 | GEO
Project description:We found NUP98 fusions activate Hoxb-associated lncRNA, HoxBlinc that occupies homeotic/oncogenic topologically associated domain (TAD) boundaries in malignant hematopoiesis. Aberration of HoxBlinc led to recruitment of MLL1 complex and reorganization of homeotic/oncogenicTADs that enhanced chromatin accessibilities and aberrantly activated homeotic/hematopoietic oncogenes defined by Hoxblinc chromatin occupancies in NUP98-PHF23 related murine leukemia cells. Eliminated HoxBlinc in NUP98 fusion-driven leukemic cells resulted in loss of Hoxblinc binding, TAD integrity, recruitment of MLL complex, and MLL driven H3K4me3 and chromatin accessibility within the HoxBlinc defined domain in a CTCF independent manner, leading to inhibiting homeotic/leukemic oncogenes and mitigating NUP98 fusion-driven leukemia in xenografted mouse models. Moreover, overexpression of HoxBlinc in mouse bone marrow hematopoietic compartment developed multiple leukemia resembling NUP98-PHF23 knock-in mice via enhancing HoxBlinc binding and TAD formation to transcriptionally expanding HS/PC and myeloid/lymphoid subpopulations leading to leukemogenesis. Our studies reveal a CTCF independent role of HoxBlinc in leukemic TAD organization and oncogenic gene regulatory networks in NUP98-fusion related leukemia.
2025-01-31 | GSE269221 | GEO
Project description:We found NUP98 fusions activate Hoxb-associated lncRNA, HoxBlinc that occupies homeotic/oncogenic topologically associated domain (TAD) boundaries in malignant hematopoiesis. Aberration of HoxBlinc led to recruitment of MLL1 complex and reorganization of homeotic/oncogenicTADs that enhanced chromatin accessibilities and aberrantly activated homeotic/hematopoietic oncogenes defined by Hoxblinc chromatin occupancies in NUP98-PHF23 related murine leukemia cells. Eliminated HoxBlinc in NUP98 fusion-driven leukemic cells resulted in loss of Hoxblinc binding, TAD integrity, recruitment of MLL complex, and MLL driven H3K4me3 and chromatin accessibility within the HoxBlinc defined domain in a CTCF independent manner, leading to inhibiting homeotic/leukemic oncogenes and mitigating NUP98 fusion-driven leukemia in xenografted mouse models. Moreover, overexpression of HoxBlinc in mouse bone marrow hematopoietic compartment developed multiple leukemia resembling NUP98-PHF23 knock-in mice via enhancing HoxBlinc binding and TAD formation to transcriptionally expanding HS/PC and myeloid/lymphoid subpopulations leading to leukemogenesis. Our studies reveal a CTCF independent role of HoxBlinc in leukemic TAD organization and oncogenic gene regulatory networks in NUP98-fusion related leukemia.
2025-01-31 | GSE269217 | GEO
Project description:We found NUP98 fusions activate Hoxb-associated lncRNA, HoxBlinc that occupies homeotic/oncogenic topologically associated domain (TAD) boundaries in malignant hematopoiesis. Aberration of HoxBlinc led to recruitment of MLL1 complex and reorganization of homeotic/oncogenicTADs that enhanced chromatin accessibilities and aberrantly activated homeotic/hematopoietic oncogenes defined by Hoxblinc chromatin occupancies in NUP98-PHF23 related murine leukemia cells. Eliminated HoxBlinc in NUP98 fusion-driven leukemic cells resulted in loss of Hoxblinc binding, TAD integrity, recruitment of MLL complex, and MLL driven H3K4me3 and chromatin accessibility within the HoxBlinc defined domain in a CTCF independent manner, leading to inhibiting homeotic/leukemic oncogenes and mitigating NUP98 fusion-driven leukemia in xenografted mouse models. Moreover, overexpression of HoxBlinc in mouse bone marrow hematopoietic compartment developed multiple leukemia resembling NUP98-PHF23 knock-in mice via enhancing HoxBlinc binding and TAD formation to transcriptionally expanding HS/PC and myeloid/lymphoid subpopulations leading to leukemogenesis. Our studies reveal a CTCF independent role of HoxBlinc in leukemic TAD organization and oncogenic gene regulatory networks in NUP98-fusion related leukemia.
2025-01-31 | GSE269216 | GEO