Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1.

PubWeight™: 1.05‹?› | Rank: Top 15%

🔗 View Article (PMC 4542316)

Published in Cell Rep on February 19, 2015

Authors

Eleni M Tomazou1, Nathan C Sheffield2, Christian Schmidl2, Michael Schuster2, Andreas Schönegger2, Paul Datlinger2, Stefan Kubicek2, Christoph Bock3, Heinrich Kovar4

Author Affiliations

1: Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, 1090 Vienna, Austria.
2: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.
3: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria; Max Planck Institute for Informatics, 66123 Saarbrücken, Germany. Electronic address: cbock@cemm.oeaw.ac.at.
4: Children's Cancer Research Institute, St. Anna Kinderkrebsforschung, 1090 Vienna, Austria; Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: heinrich.kovar@ccri.at.

Articles citing this

G-quadruplex structures mark human regulatory chromatin. Nat Genet (2016) 0.95

Dissecting the role of aberrant DNA methylation in human leukaemia. Nat Commun (2015) 0.93

LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor. Bioinformatics (2015) 0.93

A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas. Front Oncol (2015) 0.88

Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma. Oncotarget (2015) 0.85

The second European interdisciplinary Ewing sarcoma research summit - A joint effort to deconstructing the multiple layers of a complex disease. Oncotarget (2016) 0.85

Sequencing Overview of Ewing Sarcoma: A Journey across Genomic, Epigenomic and Transcriptomic Landscapes. Int J Mol Sci (2015) 0.82

Combined experience of six independent laboratories attempting to create an Ewing sarcoma mouse model. Oncotarget (2016) 0.81

Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma. Oncotarget (2016) 0.81

Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time. Biotechnol Bioeng (2016) 0.80

IGF-1R and mTOR Blockade: Novel Resistance Mechanisms and Synergistic Drug Combinations for Ewing Sarcoma. J Natl Cancer Inst (2016) 0.80

Targeting the epigenetic readers in Ewing sarcoma inhibits the oncogenic transcription factor EWS/Fli1. Oncotarget (2016) 0.78

Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting. Oncotarget (2016) 0.78

Potential approaches to the treatment of Ewing's sarcoma. Oncotarget (2016) 0.77

Loss of Ewing sarcoma EWS allele promotes tumorigenesis by inducing chromosomal instability in zebrafish. Sci Rep (2016) 0.77

Promoter Methylation Analysis Reveals That KCNA5 Ion Channel Silencing Supports Ewing Sarcoma Cell Proliferation. Mol Cancer Res (2015) 0.76

The role of miR-17-92 in the miRegulatory landscape of Ewing sarcoma. Oncotarget (2016) 0.75

Transcriptional Addiction in Cancer. Cell (2017) 0.75

Activation of Wnt/β-Catenin in Ewing Sarcoma Cells Antagonizes EWS/ETS Function and Promotes Phenotypic Transition to More Metastatic Cell States. Cancer Res (2016) 0.75

A bivalent promoter contributes to stress-induced plasticity of CXCR4 in Ewing sarcoma. Oncotarget (2016) 0.75

EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway. FEBS Lett (2016) 0.75

Tumorigenicity of Ewing sarcoma is critically dependent on the trithorax proteins MLL1 and menin. Oncotarget (2016) 0.75

Nasopharyngeal carcinoma super-enhancer-driven ETV6 correlates with prognosis. Proc Natl Acad Sci U S A (2017) 0.75

Articles cited by this

An integrated encyclopedia of DNA elements in the human genome. Nature (2012) 64.73

Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature (2013) 20.16

Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A (2010) 15.13

A unique chromatin signature uncovers early developmental enhancers in humans. Nature (2010) 14.02

Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell (2013) 9.55

DNA-binding factors shape the mouse methylome at distal regulatory regions. Nature (2011) 8.75

Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell (2013) 8.37

Super-enhancers in the control of cell identity and disease. Cell (2013) 7.50

Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods (2013) 7.06

Fusion genes and rearranged genes as a linear function of chromosome aberrations in cancer. Nat Genet (2004) 5.75

The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med (1994) 4.65

EWS/FLI-1 silencing and gene profiling of Ewing cells reveal downstream oncogenic pathways and a crucial role for repression of insulin-like growth factor binding protein 3. Mol Cell Biol (2004) 3.33

Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma. Cancer Cell (2006) 3.29

Clinical implications of the cancer genome. J Clin Oncol (2010) 3.11

Mesenchymal stem cell features of Ewing tumors. Cancer Cell (2007) 3.04

Ewing's sarcoma family of tumors: current management. Oncologist (2006) 2.97

Mapping human epigenomes. Cell (2013) 2.44

EWS-FLI-1 expression triggers a Ewing's sarcoma initiation program in primary human mesenchymal stem cells. Cancer Res (2008) 2.39

DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol Cell Biol (1994) 2.18

Leukaemogenesis: more than mutant genes. Nat Rev Cancer (2010) 2.16

EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell (2014) 2.06

The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun (2014) 1.90

The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation. PLoS Genet (2014) 1.74

A molecular function map of Ewing's sarcoma. PLoS One (2009) 1.69

Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions. Genome Res (2013) 1.69

Genomic landscape of Ewing sarcoma defines an aggressive subtype with co-association of STAG2 and TP53 mutations. Cancer Discov (2014) 1.63

Repression of the gene encoding the TGF-beta type II receptor is a major target of the EWS-FLI1 oncoprotein. Nat Genet (1999) 1.57

EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res (1993) 1.52

The genomic landscape of pediatric Ewing sarcoma. Cancer Discov (2014) 1.46

Alteration of cyclin D1 transcript elongation by a mutated transcription factor up-regulates the oncogenic D1b splice isoform in cancer. Proc Natl Acad Sci U S A (2008) 1.43

Mechanism and relevance of EWS/FLI-mediated transcriptional repression in Ewing sarcoma. Oncogene (2012) 1.20

Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome Res (2013) 1.11

Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth. Clin Cancer Res (2007) 1.04

Downstream EWS/FLI1 - upstream Ewing's sarcoma. Genome Med (2010) 1.01

New strategies in ewing sarcoma: lost in translation? Clin Cancer Res (2014) 0.81