Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA258377 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1552850.fastq.gz | Fastqsanger.gz | |||
| SRR1552860.fastq.gz | Fastqsanger.gz | |||
| SRR1552851.fastq.gz | Fastqsanger.gz | |||
| SRR1552861.fastq.gz | Fastqsanger.gz | |||
| SRR1552852.fastq.gz | Fastqsanger.gz |
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Project description:Fusion proteins involving the ETS factor ERG have been associated with multiple cancers such as Ewing's sarcoma and prostate cancer. In acute myeloid leukemias harboring t(16;21) another ERG fusion protein is expressed, FUS-ERG. Here, we found that this FUS-ERG oncofusion protein acts in the context of a heptad of proteins (ERG, FLI1, GATA2, LYL1, LNMO2, RUNX1 and TAL1) central to proper expression of genes involved in maintaining a stem cell hematopoietic phenotype. Moreover, in t(16;21) FUS-ERG co-occupies genomic regions bound by the nuclear receptor heterodimer RXR-RARA inhibiting target gene expression and interfering with hematopoietic differentiation. All-Trans Retinoic Acid treatment of t(16;21) cells as well as FUS-ERG knock down alleviate the myeloid differentiation block. Together, the results suggest that FUS-ERG acts as a transcriptional repressor of the retinoic acid signaling pathway. Cell lines were used for RNA extraction for RNA-seq and ChIP experiments for ChIP-seq.
2015-06-23 | E-GEOD-60477 | biostudies-arrayexpress
Project description:Fusion proteins involving the ETS factor ERG have been associated with multiple cancers such as Ewing's sarcoma and prostate cancer. In acute myeloid leukemias harboring t(16;21) another ERG fusion protein is expressed, FUS-ERG. Here, we found that this FUS-ERG oncofusion protein acts in the context of a heptad of proteins (ERG, FLI1, GATA2, LYL1, LNMO2, RUNX1 and TAL1) central to proper expression of genes involved in maintaining a stem cell hematopoietic phenotype. Moreover, in t(16;21) FUS-ERG co-occupies genomic regions bound by the nuclear receptor heterodimer RXR-RARA inhibiting target gene expression and interfering with hematopoietic differentiation. All-Trans Retinoic Acid treatment of t(16;21) cells as well as FUS-ERG knock down alleviate the myeloid differentiation block. Together, the results suggest that FUS-ERG acts as a transcriptional repressor of the retinoic acid signaling pathway.
2015-06-23 | GSE60477 | GEO
Project description:ERG has been identified as an essential factor for the function and maintenance of adult hematopoietic stem cells and high ERG expression is a negative prognostic marker for treatment outcome in AML. The molecular function of ERG and its interplay with other factors is however largely unknown. Here we demonstrate that ERG has cell type specific distributions in normal CD34+ myeloid progenitors and in AML cells and identify ERG as a potential pioneering protein for binding of oncofusion protein complexes. In addition, we identify H3 acetylation as the epigenetic mark preferentially associated with ERG binding. This intimate connection between ERG binding and H3 acetylation implies that one of the molecular strategies of the oncofusion proteins PML-RARa and AML1-ETO could involve the targeting of histone deacetylase activities to ETS factor bound hematopoietic regulatory sites. Examination of AML1-ETO, RUNX1, CBFb, HEB, FLI1 and ERG binding sites (ChIP-seq) in leukemic and normal hematopoietic cells, association with chromatin modifications and expression (RNA-seq) analysis of an AML1-ETO expressing cell line (SKNO-1)
2012-09-18 | E-GEOD-23730 | biostudies-arrayexpress
Project description:ERG has been identified as an essential factor for the function and maintenance of adult hematopoietic stem cells and high ERG expression is a negative prognostic marker for treatment outcome in AML. The molecular function of ERG and its interplay with other factors is however largely unknown. Here we demonstrate that ERG has cell type specific distributions in normal CD34+ myeloid progenitors and in AML cells and identify ERG as a potential pioneering protein for binding of oncofusion protein complexes. In addition, we identify H3 acetylation as the epigenetic mark preferentially associated with ERG binding. This intimate connection between ERG binding and H3 acetylation implies that one of the molecular strategies of the oncofusion proteins PML-RARa and AML1-ETO could involve the targeting of histone deacetylase activities to ETS factor bound hematopoietic regulatory sites.
2012-09-18 | GSE23730 | GEO
Project description:Stable Ba/F3 transfectants with FUS-ERG were repeatedly exposed with Aza in a clinical administration manner of 7-days treatment and 21-days interval to investigate Aza sensitivity. RNA-seq was performed when Aza susceptibility began to change and identified genes with altered expression or transcript variants.
2022-11-21 | GSE217967 | GEO
Project description:Co-targeting the plasticity and heterogeneity of cancer is fundamental to achieve and maintain complete remission (CR). We exploited murine models of acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia driven by the promyelocytic leukemia/retinoic acid receptor (PML-RARα) oncofusion protein, which recruits histone deacetylase (HDAC)-containing complexes. We investigated the effect of two HDAC inhibitors: valproic acid (VPA), and SAHA/vorinostat with all-trans retinoic acid (ATRA), on the bulk cells and LICs of two APLs with different LIC frequencies. VPA and SAHA selectively target the bulk APL cells and LICs respectively. VPA+SAHA+ATRA combination induced CR in an APL model with lower LIC frequency.
2023-02-08 | GSE196379 | GEO
Project description:Retinoic acid receptors (RARs) α, β and γ are key regulators of embryonic development. Hematopoietic differentiation is regulated by RARα, and several types of leukemia show aberrant RARα activity. We demonstrate that RARα plays an important role in cellular memory and imprinting by regulating the CpG methylation status of specific promoter regions. We used microarrays to identify genes, which display differential expression in F9 RARalpha knockout (RARaKO) cells relative to F9 wt cells. F9 teratocarcinoma cells (WT and RARaKO) were treated for 8 hours with either vehicle (EtOH) or all-trans Retinoic Acid (atRA) in the presence of the protein synthesis inhibitor Cycloheximide
2011-08-09 | E-GEOD-31280 | biostudies-arrayexpress
Project description:Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion CBF::MYH11 oncoprotein regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion. Mechanistically, we show that the NRP1 locus has open chromatin in inv(16) AML, and that CBF::MYH11 modulates the local function of the transcription factors ERG, GATA2 and RUNX1 to sustain NRP1 levels. We found that ERG activates NRP1 expression, and that CBF::MYH11 knockdown represses ERG expression, thereby allowing the repressive activity of GATA2/RUNX1 at three NRP1 enhancers. Functionally, we demonstrate that NRP1 enhances the expansion of leukemic cells in vitro and in mice, and that this activity is dependent on its VEGFR-associated FV/FVIII domain. Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy.
2024-11-18 | GSE215613 | GEO
Project description:The ERG gene belongs to the ETS family of transcription factors and has been found involved in atypical chromosomal rearrangements in several cancers. To gain insight into the oncogenic activity of ERG, we compared the gene expression profile of NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG,. We found that all the three ERG fusions significantly up-regulate PIM-1 expression in the NIH-3T3 cell line. PIM-1 is a serine/threonine kinase frequently over-expressed in cancers of haematological and epithelial origin. We show here that tERG expression induces PIM-1 in the non-malignant prostate cell line RWPE-1, strengthening the relation between tERG and PIM-1 up-regulation in the initial stages of prostate carcinogenesis. Silencing of tERG reversed PIM-1 induction. A significant association between ERG and PIM-1 expression in clinical prostate carcinoma specimens was found, suggesting that such a mechanism may be relevant in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly binds to PIM-1 promoter in the RWPE-1 prostate cell line, suggesting that tERG could be a direct regulator of PIM-1 expression. The up-regulation of PIM-1 induced by tERG over-expression significantly modified CyclinB1 levels and increased the percentage of aneuploid cells in the RWPE-1 cell line after 24hrs of taxane-based treatment. Here we provide the first evidence for an ERG-mediated PIM-1 up-regulation in prostate cells in vitro and in vivo, suggesting a direct effect of ERG transcriptional activity in the alteration of genetic stability. NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG together with the empty vector where profiled in triplicate. Quality control using NUSE and RLE plots identified one array as problematic (R540_TMP-ERG_P1) which was removed.
2011-11-30 | E-GEOD-32481 | biostudies-arrayexpress
Project description:Oncofusion protein AML1-ETO targets ERG factor binding sites in AML
| PRJNA130783 | ENA