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PROVIDER: PRJEB57218 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Shared requirement for MYC upstream super-enhancer region in tissue regeneration and cancer
| PRJNA1022134 | ENA
Project description:Super-enhancers may regulate target genes through chromatin looping. We connected super-enhancers in the K562 chronic myelogenous leukemia cell line with chromatin interactions identified from Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) data. Gene expression at proximal elements that are connected with distal super-enhancers showed significantly higher cell-type specificity than at proximal elements connected with other elements or not involved in interaction. 4C and Episwitch analysis of chromatin interactions showed that certain chromatin interactions are cell-specific, but others are more general. While super-enhancers upstream of c-MYC at the MYC-335 element can be found in other cancers, only super-enhancers downstream of c-MYC can be found in K562. 4C analysis of the c-MYC promoter revealed no chromatin interactions that are directed upstream of c-MYC, but only downstream of c-MYC, in the PVT1 long non-coding RNA gene. Cell-specific usage of super-enhancers could explain why the MYC-335 element that is associated with many solid cancers such as colorectal cancer and breast cancer, but not with leukemia. Surprisingly, we found that a chromatin interaction between c-MYC and a c-MYC super-enhancer is lost in chronic myelogenous leukemia patient blood as compared with blood from individuals without the disease through Oxford Biodynamicsâ?? Episwitch analysis. These results provide evidence for fine-tuning of expression patterns, such as cell-specific regulation of target genes by distal super-enhancers through chromatin interactions and an association between chromatin interactions and disease, and highlight that super-enhancers are more complex than previously described. Examination of several chromatin interactions involving super-enhancers using 4C-Seq and Episwitch (TM)
2017-05-01 | E-GEOD-77125 | biostudies-arrayexpress
Project description:Chromosomal rearrangements are a frequent cause of oncogene deregulation in human malignancies. Overexpression of EVI1 is found in a subgroup of acute myeloid leukemia (AML) with 3q26 chromosomal rearrangements which are often therapy resistant. In a cohort of primary t(3;8)(q26;q24) AML samples we observed the translocation of a MYC super-enhancer to EVI1. We generated a patient-based t(3;8)(q26;q24) model in vitro using CRISPR-Cas9 technology and demonstrated hyper-activation of EVI1 by the hijacked MYC super-enhancer. One MYC super-enhancer element in particular, which recruits early hematopoietic regulators, is critical for EVI1 expression and enhancer-promoter interaction. This interaction is facilitated by a CTCF-bound motif upstream of the EVI1 promoter that acts as an enhancer-docking site in t(3;8) AML. Genomic analyses of 3q26-rearranged AML samples point to a common mechanism by which EVI1 uses this CTCF-bound enhancer-docking site to hijack early hematopoietic enhancers.
| EGAS00001004808 | EGA
Project description:Super-enhancers may regulate target genes through chromatin looping. We connected super-enhancers in the K562 chronic myelogenous leukemia cell line with chromatin interactions identified from Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) data. Gene expression at proximal elements that are connected with distal super-enhancers showed significantly higher cell-type specificity than at proximal elements connected with other elements or not involved in interaction. 4C and Episwitch analysis of chromatin interactions showed that certain chromatin interactions are cell-specific, but others are more general. While super-enhancers upstream of c-MYC at the MYC-335 element can be found in other cancers, only super-enhancers downstream of c-MYC can be found in K562. 4C analysis of the c-MYC promoter revealed no chromatin interactions that are directed upstream of c-MYC, but only downstream of c-MYC, in the PVT1 long non-coding RNA gene. Cell-specific usage of super-enhancers could explain why the MYC-335 element that is associated with many solid cancers such as colorectal cancer and breast cancer, but not with leukemia. Surprisingly, we found that a chromatin interaction between c-MYC and a c-MYC super-enhancer is lost in chronic myelogenous leukemia patient blood as compared with blood from individuals without the disease through Oxford Biodynamics’ Episwitch analysis. These results provide evidence for fine-tuning of expression patterns, such as cell-specific regulation of target genes by distal super-enhancers through chromatin interactions and an association between chromatin interactions and disease, and highlight that super-enhancers are more complex than previously described.
2017-05-01 | GSE77125 | GEO
Project description:Bromodomain-containing protein 4 (BRD4) functions as an epigenetic reader and binds to so-called super-enhancer regions of driving oncogenes such as MYC in cancer. We investigated the possibility to target super-enhancer regulated genes in neuroblastoma and in MYCN amplified disease in particular. We used OTX015, the first small-molecule BRD4 inhibitor to enter clinical phase I/II trials in adults, to test the feasibility to specifically target super-enhancer regulated gene-expression in neuroblastoma. BRD4 inhibition lead to significant transcriptional down-regulation of genes that were associated with super-enhancers, supporting the notion that BRD4 preferentially acts at these chromatin sites. BRD4 inhibition not only attenuated MYCN transcription but most significantly affected MYCN-regulated transcriptional programs.
2016-07-03 | E-MTAB-3672 | biostudies-arrayexpress
Project description:Requirement for the Mediator kinase module for activation of super-enhancer associated genes in colon cancer cells
2025-01-23 | E-MTAB-5873 | ExpressionAtlas
Project description:The viewpoints used in the 4C-seq data were either the EVI1 promoter or the MYC super-enhancer
| EGAD00001006818 | EGA
Project description:Super-enhancers are principal determinants of cell transcription, development, phenotype, and oncogenesis, not yet implicated in host-pathogen interactions. We found four Epstein-Barr virus (EBV) oncoproteins and five EBV-activated NF-M-oM-^AM-+B subunits co-occupying thousand of enhancer sites in EBV-transformed lymphoblastoid cells (LCLs). Of these, 187 had markedly higher and broader histone H3K27ac signals characteristic of super-enhancer formation, and were designated M-bM-^@M-^\EBV super-enhancersM-bM-^@M-^]. EBV super-enhancer associated genes included MYC and BCL2, which enable LCL proliferation and survival. EBV super-enhancers were enriched for specific B cell transcription factor motifs and had high STAT5 and NFAT co-occupancy. EBV super-enhancer associated genes were more highly expressed than other LCL genes. Disruption of EBV super-enhancers by the bromo-domain inhibitor, JQ1, by conditional inactivation of an EBV oncoprotein or NF-M-oM-^AM-+B, decreased MYC or BCL2 gene expression and arrested LCL growth. These findings provide novel insights into the mechanisms by which EBV causes lymphoproliferation and identify opportunities for therapeutic intervention. ChIP-seq was used to define the BRD4 genome-wide landscape in GM12878 lymphoblastoid cells.
2014-11-01 | E-GEOD-62912 | biostudies-arrayexpress
Project description:Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer with high metastatic potential, limited treatment options and low patient survival rates. By combining functional proteomics and genomics approaches, we identify an oncogenic transcriptional network in mesenchymal and invasive TNBC involving the glucocorticoid receptor (GR), GATA6, MYC and AP-1 transcription factors. Although these transcription factors bind extensively to shared enhancers, they utilize different enhancer repertoires from this shared enhancer pool to drive distinct downstream oncogenic pathways. We demonstrate that the SWI/SNF chromatin remodeling complex is a common gatekeeper of chromatin access for these transcription factors, and SWI/SNF inhibition decommissions the distinct enhancer networks and pro-tumorigenic gene programs they control. Consistently, SWI/SNF inhibition blocks growth, glucocorticoid-induced chemoresistance and invasion/metastasis. Thus, we propose that SWI/SNF-mediated chromatin remodeling drives multiple hallmarks of TNBC progression, positioning SWI/SNF as a promising therapeutic target in this disease.
2025-08-27 | PXD050921 | Pride
Project description:Lymphomagenesis in the presence of deregulated MYC expression requires suppression of MYC-driven apoptosis, often through downregulation of the pro-apoptotic BCL2L11 gene (Bim). Transcription factors (EBNAs) encoded by the lymphoma-associated Epstein-Barr virus (EBV) activate MYC and silence BCL2L11. We show that EBNA2 upregulates MYC by reconfiguring the 3 Mb MYC locus to increase upstream and decrease downstream enhancer-promoter interactions. EBNA2 recruits the SWI/SNF ATPase BRG1 to drive MYC enhancer-promoter interactions. MYC-Immunoglobulin translocation breakpoints in EBV-positive endemic Burkitt lymphoma localise to EBNA2-activated upstream MYC regions. This implicates EBV in the genesis and localisation of breakpoints, since active enhancers are targeted by activation-induced cytidine deaminase. We identify a novel haematopoietic BCL2L11 enhancer hub that is inactivated by EBNA3A and EBNA3C through recruitment of the H3K27 methyltransferase EZH2. Reversal of enhancer inactivation using an EZH2 inhibitor upregulates BCL2L11 and induces apoptosis. EBV therefore drives lymphomagenesis by hijacking long-range enhancer hubs and specific cellular co-factors. A study of MYC enhancer-promoter interactions using 4C on induction of MYC by the Epstein-Barr virus transcription factor EBNA2 in a lymphoblastoid cell line.
2016-08-04 | E-GEOD-82149 | biostudies-arrayexpress