Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA294529 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide binding of MYCN protein in MYCN-amplified neuroblastoma cell lines
| PRJNA374035 | ENA
Project description:Comparison of MYCN and MECP2 genome wide binding sites in the neuroblastoma genome
2012-04-05 | E-MTAB-621 | biostudies-arrayexpress
Project description:To identify the MYCN transcription factor binding sites across the genome, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MYCN and anti-IgG antibodies on a MYCN-amplified NB cell line, SK-N-BE(2)-C. Identification of MYCN binding in neuroblastoma cells.
2016-05-16 | E-GEOD-72640 | biostudies-arrayexpress
Project description:The aim of the experiment is to identify genome wide binding sites for the transcription factor MYCN in MYCN non-amplified and MYCN amplified human neuroblastoma cell lines. Datasets are presented for the ChIP-seq analysis in the tetracycline inducible cell line SH-SY5Y-MYCN (SH-SY5Y/6TR(EU)/pTrex-Dest-30/MYCN), derivative of the parental cell line SH-SY5Y; for noninduced cells and for 24 and 48 hours of Tet induction. Analysis for patinet matched MYCN amplified cell lines SMS-KCN and SMS-KCNR is also included.
2016-10-25 | E-MTAB-4100 | biostudies-arrayexpress
Project description:Effects of MYCN knockdwon on miRNA expression in neuroblastoma cells
| PRJNA294758 | ENA
Project description:In neuroblastoma, amplification of the oncogenic basic helix-loop-helix (bHLH) transcription factor (TF) MYCN is the defining prognosticator of high-risk disease, occurs in one-third of neuroblastoma, and drastically reduces overall survival rates. As a proto-oncogene, targeted MYCN overexpression in peripheral neural crest is sufficient to initiate disease in mouse models. In MYCN amplified neuroblastoma, elevated expression of the factor is crucial to maintain tumor stemness and is associated with increased proliferation and aberrant cell cycle progression, as these tumors lack the ability to arrest in G1 in response to irradiation. MYCN down-regulation broadly reverses these oncogenic phenotypes in a variety of neuroblastoma models and recent thereapeutic strategies to indirectly target MYCN production or protein stability have reduced tumor growth in vivo. These observations motivate an investigation of MYCN binding in MYCN amplified tumors as it remains fundamentally unclear how elevated levels of the factor occupy the genome and alter transcriptional programs in neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of direct MYCN perturbation in neuroblastoma. We find that at oncogenic levels, MYCN associates with E-box (CANNTG) binding motifs in an affinity dependent manner across most active cis-regulatory promoters and enhancers. MYCN shutdown globally reduces histone acetylation and transcription, consistent with prior descriptions of MYC proteins as non-linear amplifiers of gene expression. We establish that MYCN load at the promoter and proximal enhancers predicts transcriptional responsiveness to MYCN shutdown and that MYCN enhancer binding occurs prominently at the most strongly occupied and down-regulated genes, suggesting a role for these tissue specific elements in predicating MYCN responsive âtargetâ genes. At these invaded enhancers, we identify the lineage specific bHLH TWIST1 as a key collaborator and dependency of oncogenic MYCN. These data suggest that MYCN enhancer invasion helps shape transcriptional amplification of the neuroblastoma gene expression program to promote tumorigenesis. ChIP-Seq in SHEP21, BE2C, KELLY, and NGP neuroblastoma cell lines for H3K27ac, H3K4me3, RNA PolII, MYCN, BRD4, or TWIST1
2016-09-01 | E-GEOD-80151 | biostudies-arrayexpress
Project description:Functional MYCN signature predicts outcome of neuroblastoma irrespective of MYCN amplification.
| PRJNA170239 | ENA
Project description:Amplification of MYCN plays a pivotal role in multiple types of tumors and correlates with poor prognosis in high-risk neuroblastoma. Despite recent advances in the treatment of neuroblastoma, no approaches directly target the master oncogene MYCN. Difficulties in targeting the MYCN protein have inspired us to develop a new gene level inhibitory strategy using a sequence-specific gene regulator. Here we generated a MYCN-targeting pyrrole-imidazole (PI) polyamide, MYCN-A3, which directly binds to and alkylates DNA at homing motifs within MYCN transcript. Pharmacological suppression of MYCN inhibited the proliferation of cancer cells harboring MYCN amplification compared with MYCN non-amplified cancer cells. In neuroblastoma xenograft mouse models, MYCN-A3 specifically downregulated MYCN expression and suppressed tumor progression with no detectable adverse effects and resulted in prolonged overall survival. Moreover, we observed the copy number reduction of MYCN in neuroblastoma cells with MYCN amplification upon treatment with MYCN-A3 but not MYCN non-targeting PI polyamide. Expression microarray experiments were also performed to compare the genome-wide effect of MYCN-A3 with CRISPR/Cas9 silencing of MYCN (MYCNcr-a).
2018-12-25 | GSE121529 | GEO
Project description:Amplification of MYCN plays a pivotal role in multiple types of tumors and correlates with poor prognosis in high-risk neuroblastoma. Despite recent advances in the treatment of neuroblastoma, no approaches directly target the master oncogene MYCN. Difficulties in targeting the MYCN protein have inspired us to develop a new gene level inhibitory strategy using a sequence-specific gene regulator. Here we generated a MYCN-targeting pyrrole-imidazole (PI) polyamide, MYCN-A3, which directly binds to and alkylates DNA at homing motifs within MYCN transcript. Pharmacological suppression of MYCN inhibited the proliferation of cancer cells harboring MYCN amplification compared with MYCN non-amplified cancer cells. In neuroblastoma xenograft mouse models, MYCN-A3 specifically downregulated MYCN expression and suppressed tumor progression with no detectable adverse effects and resulted in prolonged overall survival. Moreover, we observed the copy number reduction of MYCN in neuroblastoma cells with MYCN amplification upon treatment with MYCN-A3 but not MYCN non-targeting PI polyamide. Expression microarray experiments were also performed to compare the genome-wide effect of MYCN-A3 with CRISPR/Cas9 silencing of MYCN (MYCNcr-a).
2018-12-25 | GSE121528 | GEO