IRF2BP2 counteracts the ATF7/JDP2 heterodimer to prevent inflammatory overactivation in AML cells.
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ABSTRACT:
PROVIDER: PRJNA955104 | ENA |
REPOSITORIES: ENA
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Project description:Acute myeloid leukemia (AML) is a hematological malignancy characterized by the abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator that has been implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that in AML cells IRF2BP2 interacts with the transcriptional heterodimer ATF7/JDP2, which is involved to activate inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene activating function. Loss of IRF2BP2 leads to the overactivation of inflammatory pathways, resulting in immediate cell death. Our findings suggest that a delicate balance of activating and repressive transcriptional mechanisms establishes a pro-oncogenic inflammatory set-up in AML cells, and that manipulation of the ATF7/JDP2-IRF2BP2 regulatory axis may offer a potential vulnerability for AML treatment. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.
2024-05-16 | PXD041817 | Pride
Project description:Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of cell-intrinsic inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, which is involved in activating inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene-activating function. Loss of IRF2BP2 leads to overactivation of inflammatory pathways, resulting in strongly reduced proliferation. Our research indicates that a precise equilibrium between activating and repressive transcriptional mechanisms creates a pro-oncogenic inflammatory environment in AML cells. The ATF7/JDP2-IRF2BP2 regulatory axis is likely a key regulator of this process and may, therefore, represent a promising therapeutic vulnerability for AML. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.
2024-05-07 | GSE229594 | GEO
Project description:Acute myeloid leukemia (AML) is a hematological malignancy characterized by abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of cell-intrinsic inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that IRF2BP2 interacts with the AP-1 heterodimer ATF7/JDP2, which is involved in activating inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene-activating function. Loss of IRF2BP2 leads to overactivation of inflammatory pathways, resulting in strongly reduced proliferation. Our research indicates that a precise equilibrium between activating and repressive transcriptional mechanisms creates a pro-oncogenic inflammatory environment in AML cells. The ATF7/JDP2-IRF2BP2 regulatory axis is likely a key regulator of this process and may, therefore, represent a promising therapeutic vulnerability for AML. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.
2024-05-07 | GSE229593 | GEO
Project description:IRF2BP2 counteracts the ATF7/JDP2 heterodimer to prevent inflammatory overactivation in AML cells [RNA-seq]
| PRJNA955111 | ENA
Project description:IRF2BP2 counteracts the ATF7/JDP2 heterodimer to prevent inflammatory overactivation in AML cells [ChIP-seq]
| PRJNA955115 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-05-07 | GSE229595 | GEO
Project description:We report a previously unrecognized role of IRF2BP2 in neuroblastoma. To explore IRF2BP2-dependent gene regulation, RNA-seq analysis was conducted and the differently expressed genes were revealed in the IRF2BP2-knockdown SK-N-BE(2) cells in comparison to control group. We find that IRF2BP2 contributes to maintenance ADRN signature of neuroblastoma cell.
2024-06-24 | GSE236390 | GEO
Project description:Immunological memory is generally thought to be mediated exclusively by lymphocytes such as memory T and B cells. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection suggesting the presence of innate immunological memory. Here, we describe 3,811 ATF7 binding sites in mouse peritoneal macrophages, and 95% of the ATF7 signals in wild-type macrophages are lost in ATF7 knockout macrophages. ATF7 suppresses a group of innate-immunity genes in macrophage by recruiting H3K9 dimethyltransferase G9a. TLR ligands induce ATF7 phosphorylation, leading to release of ATF7 from chromatin and reduction in H3K9me2 level. Partially disrupted chromatin structure and increased basal expression on target genes are maintained for a long period, increasing resistance pathogens. Therefore we speculate ATF7 is important factor in controlling innate immunological memory. This series contains one set of whole genome ChIP-chip data and 2 sets of promoter array ChIP-chip data. For all sample, we use three IP .CEL files and three WCE .CEL files (they are triplicated experiments) to make one profile.
2015-08-31 | E-GEOD-71112 | biostudies-arrayexpress
Project description:Jdp2 is a member of the AP-1 family and suppresses histone acetyltransferase activity. We used microarrays to examine the gene expression pattern of neutrophil form Jdp2-/- mice. Bone marrow CD11b+Ly6Clo Ly6G+ neutrophils form wild-type and Jdp2-/-mice were sorted by FACS, followed by RNA extraction. Affymetrix microarrays were used to analyze the mRNA expression.
2012-11-30 | E-GEOD-42063 | biostudies-arrayexpress
Project description:Immunological memory is generally thought to be mediated exclusively by lymphocytes such as memory T and B cells. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection suggesting the presence of innate immunological memory. Here, we describe expression profile of peritoneal macrophages from wild-type mice pre-administrated with TLR ligands or from ATF7 knockout mice. ATF7 suppresses a group of innate-immunity genes in macrophage by recruiting H3K9 dimethyltransferase G9a. TLR ligands induce ATF7 phosphorylation, leading to release of ATF7 from chromatin and reduction in H3K9me2 level. Partially disrupted chromatin structure and increased basal expression on target genes are maintained for a long period, increasing resistance pathogens. Therefore we speculate ATF7 is important factor in controlling innate immunological memory. This series contains seven sets of exression array data. For all sample, we use four CEL files generated by four biological-independent experiments.
2015-08-31 | E-GEOD-71111 | biostudies-arrayexpress