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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 12, 2019 |
| Title |
BCR-ABL-mediated recruitment of STAT5 revealed by ChIPseq |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Even in the era of ABL tyrosine kinase inhibitors, eradication of chronic myeloid leukemia (CML) stem cells still remains to be a prerequisite for the complete cure of the disease. Interferon-α (IFNα), which has been used long for the treatment for CML-chronic phase, are now being re-evaluated. However, the molecular mechanism involved in the action of IFNα on CML stem cells have not been elucidated yet. In this study we have found that IFNα upregulates CCAAT/Enhancer Binding Protein β (C/EBPβ), a transcription factor required for demand-driven granulopoiesis, through activation of STAT1 and STAT5 in BCR-ABL-expressing cells. Activated STAT1 and STAT5 were recruited to the newly identified 3’ distal enhancer region of Cebpb, which contains tandemly aligned interferon-g activated sequences (GAS). Genome editing-mediated repression or deletion of the GAS elements significantly abrogated the IFNα-dependent upregulation of C/EBPβ. IFNα induces differentiation and exhaustion of CML stem cells both in vitro and in vivo in a C/EBPβ-dependent manner. In addition, IFNα upregulates C/EBPβ and induces exhaustion of CD34+ CML stem cells obtained from CML patients. Collectively, these data clearly show that C/EBPβ is a critical factor in IFNα signaling that induces differentiation and exhaustion of CML stem cells.
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| Overall design |
Examination of STAT5 binding in 3 conditions in a cell line
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| Contributor(s) |
Yokota A, Hirai H, Sato R, Adachi H, Sato F, Hayashi Y, Sato A, Kamio N, Miura Y, Nakano M, Tenen DG, Kimura S, Tashiro K, Maekawa T |
| Citation(s) |
30755436 |
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| Submission date |
Aug 18, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Hideyo Hirai |
| E-mail(s) |
hhirai@kuhp.kyoto-u.ac.jp
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| Phone |
81-75-751-3630
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| Organization name |
Kyoto University Hospital
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| Street address |
54 Kawahara-cho, Sakyo-ku
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| City |
Kyoto |
| State/province |
Kyoto |
| ZIP/Postal code |
606-8507 |
| Country |
Japan |
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| Platforms (1) |
| GPL16173 |
Illumina HiScanSQ (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA399109 |
| SRA |
SRP115808 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102809_RAW.tar |
4.5 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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