Genes and pathways involved in cellular transformation by Marek's disease oncoprotein Meq
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ABSTRACT:
ORGANISM(S): Gallus gallus
PROVIDER: GSE48454 | GEO | 2016/07/01
SECONDARY ACCESSION(S): PRJNA210198
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-01 | E-GEOD-48454 | biostudies-arrayexpress
Project description:Genes and pathways involved in cellular transformation by Marek's disease oncoprotein Meq
| PRJNA210198 | ENA
Project description:Marek's disease (MD) is an economically significant disease in chickens that is caused by the highly oncogenic Marek's disease virus (MDV). A major unanswered question is the mechanism of MDV-induced tumor formation. Meq, a bZIP transcription factor discovered in the 1990s, is critically involved in viral oncogenicity, but only a few of its host target genes have been described, impeding our understanding of MDV-induced tumorigenesis. Using chromatin immunoprecipitation-sequencing (ChIP-seq) and microarray analysis, a high-confidence list of Meq binding sites in the chicken genome and a global transcriptome of Meq-responsive genes were generated. Meq binding sites were found to be enriched in the promoter regions of upregulated genes but not in those of downregulated genes. ChIP-seq was also performed for c-Jun, a known heterodimeric partner of Meq. The close location of binding sites of Meq and c-Jun was noted, suggesting cooperativity between these two factors in modulating transcription. Pathway analysis indicated that Meq transcriptionally regulates many genes that are part of several signaling pathways including the extracellular signal-regulated kinase /mitogen-activated protein kinase (ERK/MAPK), Jak-STAT, and ErbB pathways, which are critical for oncogenesis and/or include signaling mediators involved in apoptosis. Meq activates oncogenic signaling cascades by transcriptionally activating major kinases in the ERK/MAPK pathway and simultaneously repressing phosphatases, as verified using inhibitors of MEK and ERK1/2 in a cell proliferation assay. This study provides significant insights into the mechanistic basis of Meq-dependent cell transformation.
| S-EPMC3754031 | biostudies-literature
Project description:Marek’s disease (MD) is an economically significant disease in chickens caused by the highly oncogenic Marek’s disease virus (MDV). A major unanswered question is the mechanism of MDV-induced tumor formation. Meq, a bZIP transcription factor discovered in the 1990s, is critically involved in viral oncogenicity but only a few of its host target genes have been described impeding our understanding of MDV-induced tumorigenesis. Using ChIP-seq and microarray analysis, a high confidence list of Meq-binding sites in the chicken genome and a global transcriptome of Meq-responsive genes was generated. Meq binding sites were found to be enriched in the promoter regions of up-regulated genes, but not in those of down-regulated genes. ChIP-seq was also performed for c-Jun, a known heterodimeric partner of Meq. Close location of binding sites of Meq and c-Jun was noted, suggesting cooperativity between these two factors in modulating transcription. Pathway analysis indicated that Meq transcriptionally regulates many genes that are part of several signaling pathways include the ERK/MAPK, Jak-STAT, and ErbB pathways that are critical for oncogenesis and/or include signaling mediators involved in apoptosis. Meq activates oncogenic signaling cascades by transcriptionally activating major kinases in the ERK/MAPK pathway and simultaneously repressing phosphatases, as verified using inhibitors of MEK and ERK1/2 in a cell proliferation assay. This study provides significant insights into the mechanistic basis of Meq-dependent cell transformation.
2013-05-31 | GSE47191 | GEO
Project description:Marek’s disease (MD) is an economically significant disease in chickens caused by the highly oncogenic Marek’s disease virus (MDV). A major unanswered question is the mechanism of MDV-induced tumor formation. Meq, a bZIP transcription factor discovered in the 1990s, is critically involved in viral oncogenicity but only a few of its host target genes have been described impeding our understanding of MDV-induced tumorigenesis. Using ChIP-seq and microarray analysis, a high confidence list of Meq-binding sites in the chicken genome and a global transcriptome of Meq-responsive genes was generated. Meq binding sites were found to be enriched in the promoter regions of up-regulated genes, but not in those of down-regulated genes. ChIP-seq was also performed for c-Jun, a known heterodimeric partner of Meq. Close location of binding sites of Meq and c-Jun was noted, suggesting cooperativity between these two factors in modulating transcription. Pathway analysis indicated that Meq transcriptionally regulates many genes that are part of several signaling pathways include the ERK/MAPK, Jak-STAT, and ErbB pathways that are critical for oncogenesis and/or include signaling mediators involved in apoptosis. Meq activates oncogenic signaling cascades by transcriptionally activating major kinases in the ERK/MAPK pathway and simultaneously repressing phosphatases, as verified using inhibitors of MEK and ERK1/2 in a cell proliferation assay. This study provides significant insights into the mechanistic basis of Meq-dependent cell transformation.
2016-07-01 | GSE48451 | GEO
Project description:MarekM-bM-^@M-^Ys disease (MD) is an economically significant disease in chickens caused by the highly oncogenic MarekM-bM-^@M-^Ys disease virus (MDV). A major unanswered question is the mechanism of MDV-induced tumor formation. Meq, a bZIP transcription factor discovered in the 1990s, is critically involved in viral oncogenicity but only a few of its host target genes have been described impeding our understanding of MDV-induced tumorigenesis. Using ChIP-seq and microarray analysis, a high confidence list of Meq-binding sites in the chicken genome and a global transcriptome of Meq-responsive genes was generated. Meq binding sites were found to be enriched in the promoter regions of up-regulated genes, but not in those of down-regulated genes. ChIP-seq was also performed for c-Jun, a known heterodimeric partner of Meq. Close location of binding sites of Meq and c-Jun was noted, suggesting cooperativity between these two factors in modulating transcription. Pathway analysis indicated that Meq transcriptionally regulates many genes that are part of several signaling pathways include the ERK/MAPK, Jak-STAT, and ErbB pathways that are critical for oncogenesis and/or include signaling mediators involved in apoptosis. Meq activates oncogenic signaling cascades by transcriptionally activating major kinases in the ERK/MAPK pathway and simultaneously repressing phosphatases, as verified using inhibitors of MEK and ERK1/2 in a cell proliferation assay. This study provides significant insights into the mechanistic basis of Meq-dependent cell transformation. Transcript profiling of DF-1 (a chicken embryo fibroblast cell line) and Meq-DF-1 clone 5G (DF-1 stably expressing Meq driven by the CMV promoter) using Affymetrix chicken GeneChips
2013-05-31 | E-GEOD-47191 | biostudies-arrayexpress
Project description:Marekâs disease (MD) is an economically significant disease in chickens caused by the highly oncogenic Marekâs disease virus (MDV). A major unanswered question is the mechanism of MDV-induced tumor formation. Meq, a bZIP transcription factor discovered in the 1990s, is critically involved in viral oncogenicity but only a few of its host target genes have been described impeding our understanding of MDV-induced tumorigenesis. Using ChIP-seq and microarray analysis, a high confidence list of Meq-binding sites in the chicken genome and a global transcriptome of Meq-responsive genes was generated. Meq binding sites were found to be enriched in the promoter regions of up-regulated genes, but not in those of down-regulated genes. ChIP-seq was also performed for c-Jun, a known heterodimeric partner of Meq. Close location of binding sites of Meq and c-Jun was noted, suggesting cooperativity between these two factors in modulating transcription. Pathway analysis indicated that Meq transcriptionally regulates many genes that are part of several signaling pathways include the ERK/MAPK, Jak-STAT, and ErbB pathways that are critical for oncogenesis and/or include signaling mediators involved in apoptosis. Meq activates oncogenic signaling cascades by transcriptionally activating major kinases in the ERK/MAPK pathway and simultaneously repressing phosphatases, as verified using inhibitors of MEK and ERK1/2 in a cell proliferation assay. This study provides significant insights into the mechanistic basis of Meq-dependent cell transformation. ChiP-Seq of Meq-DF-1 clone 5G (DF-1 stably expressing Meq driven by the CMV promoter) with Meq and Jun antibodies
2016-07-01 | E-GEOD-48451 | biostudies-arrayexpress
Project description:Gallid herpesvirus 2 (GaHV-2) is an oncogenic herpesvirus that causes T lymphoma in chicken. GaHV-2 encodes a basic leucine zipper (bZIP) protein of the AP-1 family, Meq. Upon formation of homo- or heterodimers with c-Jun, Meq may modulate the expression of viral and cellular genes involved in lymphomagenesis. GaHV-2 also encodes viral microRNAs (miRNAs) involved in latency and apoptosis escape. However, little is known about cellular miRNA deregulation during the development of GaHV-2-associated lymphoma. We determined the cellular miRNA expression profiles of chickens infected with a very virulent strain (RB-1B) or a vaccine strain (CVI988) or noninfected. Among the most deregulated cellular miRNAs, we focused our efforts on gga-miR-21, which is upregulated during GaHV-2 infection. We mapped the gga-miR-21 promoter to the 10th intron of the TMEM49 gene and found it to be driven by AP-1- and Ets-responsive elements. We show here that the viral oncoprotein Meq binds to this promoter, thereby transactivating gga-miR-21 expression. We confirmed that this miRNA targets chicken programmed death cell 4 (PDCD4) and promotes tumor cell growth and apoptosis escape. Finally, gga-miR-21 was overexpressed only during infection with a very virulent strain (RB-1B) and not during infection with a nononcogenic strain (CVI988), providing further evidence for its role in GaHV-2 lymphomagenesis. Our data therefore suggest an additional role for Meq in GaHV-2-mediated lymphomagenesis through the induction of miR-21 expression.
| S-EPMC3536390 | biostudies-literature
Project description:Marek's disease (MD) is a neoplastic disease of poultry caused by Marek's disease virus (MDV), a highly contagious alphaherpesvirus. Meq, the major MDV oncoprotein, induces neoplastic transformation of T-cells through several mechanisms, including inhibition of apoptosis. In contrast, the chicken anemia virus (CAV)-encoded protein apoptin (VP3) is a powerful inducer of apoptosis of tumor cells, a property that is exploited for anticancer therapeutics. Although the molecular mechanisms of selective induction of tumor cell apoptosis by apoptin are not fully understood, its tumor cell-restricted nuclear translocation is thought to be important. Co-infection with MDV and CAV is common in many countries, CAV antigens are readily detectable in MD lymphomas, and the MDV-transformed T-lymphoblastoid cell lines such as MSB-1 is widely used for propagating CAV for vaccine production. As MDV-transformed cell lines express high levels of Meq, we examined here whether CAV-encoded apoptin interacts with Meq in these cells. Using immunofluorescence microscopy, we found that apoptin and Meq co-localize to the nucleus, and biochemical analysis indicated that the two proteins do physically interact. Using a combination of Meq mutagenesis and co-immunoprecipitation, we demonstrate that apoptin interacts with Meq within a region between amino acids 130 and 140. Results from the IncuCyte assay suggested that Meq inhibits apoptin-induced apoptosis activity. In summary, our findings indicate that Meq interacts with and inhibits apoptin. Insights into this novel interaction between Meq and apoptin will relevance for pathogenesis of coinfections of the two viruses and in CAV vaccine production using MDV-transformed cell lines.
| S-EPMC6034753 | biostudies-literature
Project description:Marek's disease virus (MDV) encodes a basic-leucine zipper (BZIP) protein, Meq, which is considered the major MDV oncoprotein. It has been reported that the oncogenicity of Meq is associated with its interaction with C-terminal binding protein 1 (CtBP), which is also an interaction partner of Epstein-Barr virus encoded EBNA3A and EBNA3C oncoproteins. Since both EBNA3C and CtBP interact with histone deacetylase 1 (HDAC1) and HDAC2, we examined whether Meq shares this interaction with chicken HDAC1 (chHDAC1) and chHDAC2. Using confocal microscopy analysis, we show that Meq co-localizes with chHDAC1 and chHDAC2 in the nuclei of MDV lymphoblastoid tumor cells. In addition, immunoprecipitation assays demonstrate that Meq interacts with chHDAC1 and chHDAC2 in transfected cells and MDV lymphoblastoid tumor cells. Using deletion mutants, interaction domains were mapped to the N-terminal dimerization domain of chHDAC1 and chHDAC2, and the BZIP domain of Meq. Our results further demonstrate that this interaction mediates the degradation of chHDAC1 and chHDAC2 via the proteasome dependent pathway. In addition, our results show that Meq also induces the reduction of global ubiquitinated proteins through a proteasome dependent pathway. In conclusion, our results provide evidence that Meq interacts with chHDAC1 and chHDAC2, and induces their proteasome dependent degradation.
| S-EPMC7803728 | biostudies-literature