Glucocorticoids delay RAF-induced senescence promoted by EGR1
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ABSTRACT:
PROVIDER: PRJNA556258 | ENA |
REPOSITORIES: ENA
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Project description:Glucocorticoids delay RAF-induced senescence promoted by EGR1 [ChIP-seq]
| PRJNA556815 | ENA
Project description:Analysis of the transcriptional response to treatment with glucocorticoids in human fibroblasts entering oncogene-induced senescence.
2019-08-27 | GSE134747 | GEO
Project description:Analysis of the differential binding of EGR1 to chromatin in human fibroblasts entering oncogene-induced senescence, with and without clobetasol.
2019-08-27 | GSE134924 | GEO
Project description:In this study we used CRISPR/Cas9 to generate KO clones of the HEK-RAF-ER cell line that lack expression of EGR1, FOS and profiled the transcriptome after inducing RAF/MAPK signaling.
2024-01-13 | GSE250532 | GEO
Project description:Human bone marrow stromal cells (BMSCs) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key BMSC functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key BMSC regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSCs, downregulated upon culture, and lower in non-CFU-F-containing CD45neg BM cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSCs. Accordingly, EGR1 overexpression markedly decreased BMSC proliferation but considerably improved hematopoietic stroma support function as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement of BMSC stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. On the other hand, EGR1 knockdown increased ROS-mediated BMSC proliferation, and clearly reduced BMSC hematopoietic stroma support potential. These findings thus show that EGR1 is a key BMSC transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to coordinate the specific functions of BMSC in their different biological contexts.
2019-06-27 | PXD011767 | Pride
Project description:Previous studies have revealed that UV-stimulation of a variety of cells leads to activation of the EGF receptor, induction of Egr1, growth inhibition and apoptosis. On the other hand both Egr1 and EGF receptor activation are implicated in promoting the progression of prostate cancer. We treated M12 tumorigenic prostate epithelial cells which express little Egr1 with UV irradiation which rapidly activated the EGF receptor and elevated Egr1. Treatment with specific EGFR and ERKI/II inhibitors (PD153035 and UO126, respectively) confirmed that the upregulation of Egr1 was downstream of EGFR and ERKI/II Map kinase pathway. ChIP on chip experiments using Egr1 antibody identified 288 significantly bound promoters upon UV stimulation. Of these target genes, 40% had consensus Egr1 site in their promoters, considerably greater than that expected by chance (p < 0.005). The array binding results were validated by PCR analysis of 25 genes using DNA from conventional IP experiment. Affymetrix gene expression analysis of UV treated and control cells confirmed that a significant number of these bound promoters showed gene expression changes. Addition of siRNA to Egr1 confirmed that the gene expression changes were dependent upon Egr1 expression. Addition of EGF led to similar expression changes for nine tested genes. Proliferation and apoptosis assays confirmed that M12 cells undergo growth arrest and apoptosis following UV irradiation. Moreover, addition of EGF also promoted significant growth inhibition. These results indicate the M12 cells undergo a EGF receptor dependent apoptosis response upon UV-stimulation and that Egr1 mediates the regulation of numerous genes downstream of the EGF receptor that are associated with this response. Keywords: UV treatment analysis duplicated experiment for Affymetrix gene expression analysis and Chip-on-Chip analysis.
2010-05-06 | E-GEOD-10585 | biostudies-arrayexpress
Project description:To gain insight into the function of DNA-PKcs within immune cells, we performed a quantitative phosphoproteomic screen in T cells to identify first order phosphorylation targets of DNA-PKcs. Results indicate that DNA-PKcs phosphorylates the transcription factor Egr1 (early growth response protein 1) at S301. Expression of Egr1 is induced early upon T cell activation and dictates T cell response by modulating expression of cytokines and key costimulatory molecules. Mutation of serine 301 to alanine via CRISPR-Cas9 resulted in increased proteasomal degradation of Egr1 and a decrease in Egr1-dependent transcription of IL2 (interleukin-2) in activated T cells. Our findings identify DNA-PKcs as a critical intermediary link between T cell activation and T cell fate and a novel phosphosite involved in regulating Egr1 activity.
2021-12-21 | PXD026352 | Pride
Project description:EGR1-mediated ibrutinib resistance
| PRJNA925145 | ENA
Project description:Therapy-related myeloid neoplasms (t-MN) share many similarities with AML de novo in the elderly. One common factor is that they arise in the setting of chronic inflammation, likely due to advanced age or chemotherapy-induced senescence. Here, we examined the impact of haploinsufficient loss of the del(5q) tumor suppressor gene, EGR1, commonly deleted in high-risk MNs. In mice, under the exogenous inflammatory stress of either serial transplant or successive doses of the alkylating agent ENU, Egr1-haploinsufficient hematopoietic stem cells (HSCs) exhibit a clonal advantage. Complete loss of EGR1 function is incompatible with transformation; mutations of EGR1 are rare and are not observed in the remaining allele in del(5q) patients and complete knockout of Egr1 in mice leads to HSC exhaustion. Using chromatin immunoprecipitation sequencing (ChIP-seq), we identify EGR1 binding sites in human CD34+ cord blood-derived stem and progenitor cells (HSPCs) and show that EGR1 binds genes critical for stem cell differentiation, inflammatory signaling, and the DNA damage response. Notably, in the chromosome 5 sequences frequently deleted in patients, there is a significant enrichment of innate and inflammatory genes, which may confer a fitness advantage in an inflammatory environment. Short hairpin RNA (shRNA) mediated silencing of EGR1 biases HSPCs towards a self-renewal transcriptional signature. In the absence of EGR1, cells upregulate MYC-driven proliferative signals, downregulate CDKN1A (p21), disrupt the DNA damage response, and downregulate inflammation - adaptations anticipated to confer a relative fitness advantage for stem cells especially in an environment of chronic inflammation.
2022-09-01 | GSE184931 | GEO
Project description:We established two representative ABC DLBCL cell lines (TMD8 and OCI-Ly10) with ibrutinib resistance by gradually increasing the concentration of ibrutinib during passage in culture. RNA-seq analysis demonstrated that the BCR pathway gene signature is enriched in resistant cell lines when compared to parental cells. The most upregulated gene is EGR1, a transcription factor that activates multiple oncogenic pathways including MYC and E2F. Elevated EGR1 expression is also observed in ibrutinib-resistant primary mantle cell lymphoma cells when treated with ibrutinib. Using multiple metabolic and genetic approaches, we discovered that overexpression of EGR1 causes metabolic reprogramming to oxidative phosphorylation (OXPHOS) and ibrutinib resistance. Mechanistically, EGR1 mediates metabolic reprogramming through transcriptional activation of PDP1, a phosphatase that dephosphorylates and activates the E1 component of the large pyruvate dehydrogenase complex. Therefore, EGR1-mediated PDP1 activation accelerates intracellular ATP production via the mitochondrial tricarboxylic acid (TCA) cycle, leading to sufficient energy to enhance the proliferation and survival of ibrutinib-resistant lymphoma cells. Finally, we demonstrate that targeting OXPHOS with IM156, a newly developed OXPHOS inhibitor, inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in patient-derived xenograft mouse models.
2023-12-06 | GSE223150 | GEO