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| Status |
Public on Jul 18, 2019 |
| Title |
Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.
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| Overall design |
ChIP-seq was performed with mouse EWS/ATF1-induced sarcoma cell line (G1297), Ebf1- and Nanog-KRAB-introduced G1297 and sarcoma iPSC-derived MEF(sarcoma MEF). Total 9 samples (5 ChIP/ 4 input) were analized. In G1297 and its derivatives, we can induce EWS/ATF1 by Doxycycline (Dox)-inducible expression system. We compared binding pattern of EWS/ATF1 after Dox treatment between G1297 and sarcoma MEF, Ebf1-KRAB-introduced-G1297 and Nanog-KRAB-introduced G1297.
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| Contributor(s) |
Komura S, Itakura F, Yamada Y |
| Citation missing |
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| Submission date |
Jan 25, 2016 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Yasuhiro Yamada |
| E-mail(s) |
yasu@ims.u-tokyo.ac.jp
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| Organization name |
University of Tokyo
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| Department |
Institute of Medical Science
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| Lab |
Division of Stem Cell Pathology
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| Street address |
4-6-1, Shirokanedai, Minato-ku
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| City |
Tokyo |
| ZIP/Postal code |
108-8639 |
| Country |
Japan |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE77205 |
Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas |
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| Relations |
| BioProject |
PRJNA312285 |
| SRA |
SRP071136 |
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