Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Joseph Wiemels
PROVIDER: E-GEOD-52655 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Data from "Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein" to be published in PLOS One, authors Christofer Diakos, Yuanyuan Xiao, Shichun Zheng, Leo Kager, Michael Dworzak, Joseph L. Wiemels The experiment showed direct targets of the fusion protein. In the manuscript, individual gene targets are explained, along with DNA motifs that the fusion protein bound to. Demonstrates the "direct" targets of the E2A-PBX1 leukemia fusion protein, which is a feature of about 5% of all chilldhood leukemia. Comparison of the ChIP pull-down from E2A antibody in an E2A-PBX1 positive cell line, compared to the input DNA. There are 3 replicate experiments
2013-11-23 | E-GEOD-52653 | biostudies-arrayexpress
Project description:There is increasing evidence that microRNA and transcription factors interact in an instructive fashion in normal and malignant hematopoiesis. We explored the impact of TEL-AML1 (ETV6-RUNX1), the most common fusion protein in childhood leukemia, on miRNA expression and the leukemic phenotype. Using RNA interference, miRNA expression arrays, and quantitative PCR, we identified miRNA-494 and miRNA-320a to be upregulated upon TEL-AML1 silencing independently of TEL expression. Chromatin immunoprecipitation analysis identified miRNA-494 as a direct miRNA target of the fusion protein TEL-AML1. Using bioinformatic analysis as well as functional luciferase experiments we demonstrate that survivin is a target of the two miRNAs. MiRNA-494 and -320a were introduced to the cells by transfection and survivin expression determined by western blot analysis. These miRNAs blocked survivin expression and resulted in apoptosis in a similar manner as TEL-AML1 silencing by itself; this silencing was also shown to be DICER-dependent. MiRNAs-494 and -320a are expressed at lower levels in TEL-AML1+ leukemias compared to immunophenotype-matched non-TEL-AML1 ALL subtypes, and within TEL-AML1+ leukemias their expression is correlated to survivin levels. In summary our data suggest that TEL-AML1 might exert its anti-apoptotic action at least in part by suppressing miRNA-494 and miRNA-320a, lowering their expression causing enhanced survivin expression. DNAs from REH cells were pulled down using ChIP antibodies to TEL and hybridized to microRNA promoter tiling arrays.
2010-08-28 | E-GEOD-23842 | biostudies-arrayexpress
Project description:The presence of acetylated histone H3K56 in human embryonic stem cells (ESCs) correlates positively with the binding of Nanog, Sox2 and Oct4 (NSO) transcription factors at their target gene promoters. However, the function of H3K56ac there has been unclear. We now report that Oct4 interacts with K56ac and it is functionally important since K56ac combines with NSO factors in ChIP-Seq to mark the regions associated with pluripotency better than NSO alone. Therefore, our data suggest that K56ac plays a critical role in binding to Oct4 to promote the pluripotency of ESCs. Genome wide location analysis ChIP-Seq was performed in mouse embryonic stem cell lines (E14Tg2a) for histone H3K56ac.
2013-06-25 | E-GEOD-47387 | biostudies-arrayexpress
Project description:We investigated genome wide distribution of H3K36me2, H3K36me3 and H3K27me3 in the presence and absence of MMSET protein. MMSET overexpression in t(4;14)+ myeloma leads to global loss redistribution of H3K36me2 and genome-wide loss of H3K27 methylation. Despite the gloal decrease in H3K27me3, specific regions of the genome show enhanced H3K27me3 enrichment through increased recruitment of EZH2 methyltransferase ChIP-seq for H3K36me2, H3K36me3 and H3K27me3 in two cell types
2014-09-01 | E-GEOD-57977 | biostudies-arrayexpress
Project description:In vivo crosslinking studies suggest that the Drosophila transcription factor Bicoid (Bcd) binds to several thousand sites during early embryogenesis, but it is not clear how many of these binding events are functionally important. In contrast, reporter gene studies have identified more than 60 Bcd-dependent enhancers, all of which contain clusters of the consensus binding sequence TAATCC. These studies also identified clusters of TAATCC motifs (inactive fragments) that failed to drive Bcd-dependent activation. In general, active fragments showed higher levels of Bcd-binding in vivo, and were enriched in predicted binding sites for the ubiquitous maternal protein Zelda (Zld). Here we test the role of Zld in Bcd-mediated binding and transcription. Removal of Zld function and mutations in Zld sites caused significant reductions in Bcd-binding to known enhancers, and variable effects on the activation and spatial positioning of Bcd-dependent expression patterns. Genome-wide binding experiments in Zld mutants showed variable effects on Bcd-binding peaks, ranging from strong reductions to significantly enhanced levels of binding. Increases in Bcd binding caused the precocious Bcd-dependent activation of genes that are normally not expressed in early embryos, suggesting that Zld controls the genome-wide binding profile of Bcd at the qualitative level, and is critical for selecting target genes for activation in the early embryo. These results underscore the importance of combinatorial binding in enhancer function, and provide data that will help predict regulatory activities based on DNA sequence. 1-3 hour wild type and zelda mutant embryos were examined for Bicoid binding using Illumina HiSeq 2000. The Bcd antibody is a rabbit polyclonal antiserum raised against full length Drosophila Bcd protein (Ochoa-Espinosa et al. 2009 PNAS). The antiserum was further purified using the Protein A Antibody Purification Kit (Sigma) for ChIP-seq.
2014-05-02 | E-GEOD-55256 | biostudies-arrayexpress
Project description:Sustained or repeated exposure to sedating drugs such as alcohol triggers homeostatic adaptations in the brain that lead to the development of drug tolerance and dependence. These adaptations involve long-term changes in the transcription of drug-responsive genes as well as an epigenetic restructuring of chromosomal regions that is thought to signal and maintain the altered transcriptional state. Drug-induced epigenetic changes have been shown to be important in the long-term adaptation that leads to alcohol tolerance and dependence endophenotypes. A major constraint impeding progress is that alcohol produces a surfeit of changes in gene expression, most that may not make any meaningful contribution to the ethanol response under study. Here we used a novel genomic epigenetic approach to find genes relevant for functional alcohol tolerance by exploiting the commonalities of two chemically distinct drugs. In Drosophila melanogaster, ethanol and benzyl alcohol induce mutual cross-tolerance, indicating that they share a common mechanism for producing tolerance. We surveyed the genome-wide changes in histone acetylation that occur in response to these drugs. Each drug induces modifications in a large number of genes. The genes that respond similarly to either treatment, however, represent a subgroup enriched for genes important for the common tolerance response. Genes were functionally tested for behavioral tolerance to the sedative effects of ethanol and benzyl alcohol using mutant and inducible RNAi stocks. We identified a network of genes that are essential for the development of tolerance to sedation by alcohol. A total of six samples. Two H4Ac ChIP-chip biological replicates from heads of Drosophila (untreated, IP/input), two H4Ac ChIP-chip biological replicates from heads of Drosophila sedated with benzyl alcohol (IP_treated/IP_control), and two H4Ac ChIP-chip biological replicates from heads of Drosophila sedated with ethanol (IP_treated/IP_control) are included.
2013-09-05 | E-GEOD-48449 | biostudies-arrayexpress
Project description:Most metazoan promoters have RNA polymerase II (Pol II) paused slightly downstream of the transcription start site by NELF and DSIF. This pausing keeps these promoters available for rapid induction by P-TEFb, whose activity causes NELF to dissociate and Pol II and DSIF to elongate on the gene. ChIP-Seq data was generated for Pol II, NELF, and DSIF in HeLa cells and used to look at pausing downstream of unannotated promoters. 3x ChIP-Seq (Pol II, NELF, DSIF) in HeLa cells
2014-02-01 | E-GEOD-53008 | biostudies-arrayexpress
Project description:In this study, we used quantitative proteomics mass spectrometry with 16-plex TMT labeling to compare individual protein levels of DMSO and 1 μM CSN5i-3-treated K562 cells for 2, 8, and 24 hours. CSN5i-3 is a selective and potent inhibitor of Cop9 Signalosome (CSN), which regulates the activity of Cullin-RING E3 ubiquitin ligases (CRLs). CSN5i-3 treatment resulted in reduced CSN activity, and consequently increased cullin neddylation and constitutively active CRL. Gene Ontology analysis of the changed proteins between DMSO- and CSN5i-3-treated samples showed the enrichment of CSN subunits, cell cycle and chromosome-related components, and phosphatase complex, which include multiple CSN subunits (e.g., CSN7B and CSN5), components of CRLs, especially CRL SRs (e.g., SKP2, ELOA and DCAF1/VPRBP), and known substrates of CRLs (e.g., MAGEA6, GLUL, and RHOB). Indeed, eight out of the top 20 most decreased proteins were CRL adaptor and substrate receptors, two out of the top 20 were E2 proteins (CDC34/UBE2R1 and UBE2R2), and two were CSN subunits. Eight out of the top 20 most increased proteins were reported CRL substrates.
2022-09-05 | PXD027862 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-27 | E-GEOD-57822 | biostudies-arrayexpress
Project description:We found that MCF7 and ZR751 Sox2-expressing breast cancer cell lines comprise of cells with heterogeneous Sox2 transcription activity reporter response. A small subset of Sox2 reporter responsive cells are more tumourigenic than the bulk Sox2 reporter unresponsive cells. We questioned whether Sox2 exhibit differential gene promoter occupancies in the two cell subsets to govern differential gene expression patterns. Sox2 ChIP in reporter unresponsive (RU) and reporter responsive (RR) cells (duplicate samples) were compared. IgG ChIP in RU and RR cells served as the negative controls.
2014-09-25 | E-GEOD-61703 | biostudies-arrayexpress