Whole RNA sequencing to identify targets of ets-4 that are responsible for rege-1 (C30F12.1) phenotype
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE75160 | GEO | 2016/10/18
SECONDARY ACCESSION(S): PRJNA302661
REPOSITORIES: GEO
Similar Datasets
Project description:Deregulated expression of ETS transcription factors with oncogenic and tumor suppressor function occurs frequently in prostate cancer leading to profound alterations of the cancer transcriptome. By integrating genomic and functional studies we identified key targets of the aberrantly expressed ETS factors, ERG and ESE3. Altered expression of ETS factors led to the induction of the polycomb group protein EZH2 and silencing of the tumor suppressor Nkx3.1. Nkx3.1 was controlled by ERG and ESE3 both directly via binding to ETS binding sites in the gene promoter and indirectly via EZH2-induced histone H3K27 methylation. This may represent a general mechanism linking aberrantly expressed ETS with deregulation of epigenetic pathways and global reprogramming of the prostate epithelial cell transcriptome in prostate tumorigenesis. Keywords: prostate cancer, gene expression profiling, ETS genes In this study we show that deregulated expression of ETS factors with opposite functions is highly frequent in prostate cancer. Our study uncovers a previously unrecognized link between aberrant expression of ETS factors, deregulation of epigenetic pathways and silencing of tumor suppressor genes in prostate cancer and shows that partially distinct transcriptional programs are associated with different ETS gene expression patterns. The presence of distinct prostate cancer subgroups with different biological features may have important clinical implications and suggests that assessment of ETS expression levels might be useful to distinguish tumors with different clinical outcome.
2010-06-09 | E-GEOD-14206 | biostudies-arrayexpress
Project description:Deregulated expression of ETS transcription factors with oncogenic and tumor suppressor function occurs frequently in prostate cancer leading to profound alterations of the cancer transcriptome. By integrating genomic and functional studies we identified key targets of the aberrantly expressed ETS factors, ERG and ESE3. Altered expression of ETS factors led to the induction of the polycomb group protein EZH2 and silencing of the tumor suppressor Nkx3.1. Nkx3.1 was controlled by ERG and ESE3 both directly via binding to ETS binding sites in the gene promoter and indirectly via EZH2-induced histone H3K27 methylation. This may represent a general mechanism linking aberrantly expressed ETS with deregulation of epigenetic pathways and global reprogramming of the prostate epithelial cell transcriptome in prostate tumorigenesis. Keywords: prostate cancer, gene expression profiling, ETS genes
2010-05-25 | GSE14206 | GEO
Project description:Whole RNA sequencing to identify targets of ETS-4 and REGE-1
| PRJNA302658 | ENA
Project description:ETS-domain proteins are a family of evolutionarily conserved transcription factors (TFs) critical in the development of various cancers. Despite their recognized role in oncogenesis, the proteomic landscape of ETS family members remains underexplored. This study focuses on the systematic analysis of high-throughput proteomics data to decode the protein-protein interaction (PPI) networks and signal transduction pathways regulated by ETS factors in human cellular systems. Our findings uncover key PPIs that highlight both the redundancy and specificity of ETS family proteins, with a particular emphasis on their cooperative interactions with the MYC oncogene. These shared protein networks are strongly implicated in the pathogenesis of kidney renal clear cell carcinoma (KIRC) and other cancer types. By identifying key ETS-regulated proteins, we offer insights into novel molecular mechanisms that hold potential for therapeutic targeting. This proteomics-based approach enhances our understanding of ETS family proteins' regulatory roles, laying the groundwork for future research into oncogenic pathways and their implications in clinical oncology.
2024-10-15 | MSV000096095 | MassIVE
Project description:The tumor suppressor transcription factor p53 is mutated in nearly 50% of all cancer cases, and this frequency increases with stage and resistance to therapy. Hotspot p53 mutations lose direct DNA binding activity while gaining oncogenic function. These structural p53 mutants can bind to new regions of the genome via interactions with other transcription factors. One example is the ETS transcription factor ETS2, which was previously reported to bind mutant p53. Yet, a comprehensive understanding of mutant p53 association with the ETS family needs to be understood. Here, we compare mutant p53 interaction across 26 ETS transcription factors. Mutant p53 bound ETS proteins better than wild-type p53. All ETS proteins tested bound to mutant p53 to some extent, yet relative binding differed. The ETS DNA binding domain provided a common interaction interface, but strong binding required a second interaction domain. Genome-wide mapping found that the ETS protein ERG could recruit mutant p53 to regulatory regions of genes necessary for morphogenesis, locomotion, and androgen response in prostate cancer cells. Lastly, ETS factors that interact strongly with mutant p53 tend to be upregulated in p53 mutant ovarian cancer. These results suggest that multiple ETS proteins can work with mutant p53 in cancer.
2024-06-28 | GSE270925 | GEO
Project description:Chromatin immunoprecipitation coupled with microarray analysis (ChIP-chip) was carried out to identify new target genes for ETS-domain transcription factor Elk-1. Experiment was done in Hela cells under serum starved conditions.
2009-08-11 | E-MEXP-1527 | biostudies-arrayexpress
Project description:Aberrant overexpression of oncogenic ETS factors through chromosomal rearrangments is the most common genomic event in primary prostate tumor and these factors have been well studied. Loss of ELF1, another ETS transcription factor family member, is a common event in prostate cancer, but the function of ELF1 has not been described within the prostate. Studies of ELF1 in different tissue types has determined that it can be important for oncogeneis or tumor suppression. Here, we show that ELF1 is a novel prostate tumor suppressor by hindering oncogenic ETS function at cell migration related genes, but also that ELF1 has the ability to regulate senescence and chemotherapy resistance. Next generation sequencing was used to determine gene expression changes in RWPE-1 cells upon addition of an oncogenic ETS factor and then with the loss of ELF1 through an shRNA knockdown. Genomic binding locations were also determined for ELF1 and ERG, through ChIP-seq to identify any cobound or unique regions. The combination of this data indicates that ELF1 repressed migration related genes which ERG activates, but ELF1 also uniquely binds genes related to cell senescence and activates their transcription. There, these data indicate a novel tumor suppressive mechanism for ELF1 within the prostate and better characterizes its function within this cell type.
2018-07-01 | GSE113485 | GEO
Project description:Aberrant overexpression of oncogenic ETS factors through chromosomal rearrangments is the most common genomic event in primary prostate tumor and these factors have been well studied. Loss of ELF1, another ETS transcription factor family member, is a common event in prostate cancer, but the function of ELF1 has not been described within the prostate. Studies of ELF1 in different tissue types has determined that it can be important for oncogeneis or tumor suppression. Here, we show that ELF1 is a novel prostate tumor suppressor by hindering oncogenic ETS function at cell migration related genes, but also that ELF1 has the ability to regulate senescence and chemotherapy resistance. Next generation sequencing was used to determine gene expression changes in RWPE-1 cells upon addition of an oncogenic ETS factor and then with the loss of ELF1 through an shRNA knockdown. Genomic binding locations were also determined for ELF1 and ERG, through ChIP-seq to identify any cobound or unique regions. The combination of this data indicates that ELF1 repressed migration related genes which ERG activates, but ELF1 also uniquely binds genes related to cell senescence and activates their transcription. There, these data indicate a novel tumor suppressive mechanism for ELF1 within the prostate and better characterizes its function within this cell type.
2018-07-01 | GSE113484 | GEO
Project description:The ets transcription factor ELF5 specifies the differentiation of mammary progenitor cells to establish the milk-secreting lineage. ER- and poor prognosis basal breast cancers arise from this progenitor cell and these cancers express high levels of Elf5. Knockdown of ELF5 expression in basal breast cancer cell lines, or forced expression in luminal breast cancer cell lines, resulted in reduced cell proliferation. Transcript profiling and chromatin immunoprecipitation revealed that the transcriptional activity of ELF5 specified the gene expression patterns that distinguish basal from luminal breast cancer, including suppression of FOXA1, GATA3 and ER, key estrogen-action genes. Tamoxifen treatment of luminal MCF7 cells upregulated Elf5 expression and cells that acquired resistance to Tamoxifen became dependent on ELF5 for proliferation. ELF5 is a regulator of breast cancer cell proliferation, transcriptionally specifies the basal molecular subtype and is utilised by ER+ breast cancer cells to escape proliferative arrest caused by Tamoxifen. Elf5 was induced via doxycycline treated PyMT mouse tumours, in triplicate
2014-01-13 | E-GEOD-30406 | biostudies-arrayexpress
Project description:<p>Half of prostate cancers harbor gene fusions between <i>TMPRSS2</i> and members of the <i>ETS</i> transcription factor family. To date little is known about the presence of non-ETS fusion events in prostate cancer. We employed next-generation transcriptome sequencing (RNA-Seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes <i>ETV1</i> and <i>ERG</i>, and five involving non-ETS genes such as <i>CDKN1A</i> (p21), <i>CD9</i> and <i>IKBKB</i> (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene <i>RSRC2</i>. The novel gene fusions are found to be of low frequency but interestingly, the non-ETS fusions were all present in prostate cancer harboring the <i>TMPRSS2-ERG</i> gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement prone phenotype.</p>
| phs000310 | dbGaP