Diagenode

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


Tomazou EM, Sheffield NC, Schmidl C, Schuster M, Schönegger A, Datlinger P, Kubicek S, Bock C, Kovar H

Transcription factor fusion proteins can transform cells by inducing global changes of the transcriptome, often creating a state of oncogene addiction. Here, we investigate the role of epigenetic mechanisms in this process, focusing on Ewing sarcoma cells that are dependent on the EWS-FLI1 fusion protein. We established reference epigenome maps comprising DNA methylation, seven histone marks, open chromatin states, and RNA levels, and we analyzed the epigenome dynamics upon downregulation of the driving oncogene. Reduced EWS-FLI1 expression led to widespread epigenetic changes in promoters, enhancers, and super-enhancers, and we identified histone H3K27 acetylation as the most strongly affected mark. Clustering of epigenetic promoter signatures defined classes of EWS-FLI1-regulated genes that responded differently to low-dose treatment with histone deacetylase inhibitors. Furthermore, we observed strong and opposing enrichment patterns for E2F and AP-1 among EWS-FLI1-correlated and anticorrelated genes. Our data describe extensive genome-wide rewiring of epigenetic cell states driven by an oncogenic fusion protein.

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Antibody
H3K4me3 (C15410003)
H3K27me3 (C15410195)

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Published
February, 2015

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Products used in this publication

  • cut and tag antibody icon
    C15410196
    H3K27ac Antibody
  • cut and tag antibody icon
    C15410195
    H3K27me3 Antibody
  • ChIP-seq Grade
    C15410192
    H3K36me3 Antibody
  • cut and tag antibody icon
    C15410194
    H3K4me1 Antibody
  • cut and tag antibody icon
    C15410003-50
    H3K4me3 Antibody
  • cut and tag antibody icon
    C15410193
    H3K9me3 Antibody
  • ChIP kit icon
    C01010051
    iDeal ChIP-seq kit for Histones

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