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| Status |
Public on Feb 19, 2019 |
| Title |
Destabilization of AETFC through C/EBPalpha-mediated repression of LYL1 contributes to t(8;21) leukemic cell differentiation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
In t(8;21) leukemic cells, the leukemogenic fusion protein AML1-ETO is stabilized and functions through the AML1-ETO-containing transcription factor complex (AETFC). Destabilization of AETFC thus provides a strategy to target AML1-ETO. In this study, we found that AETFC can be destabilized by a specific mechanism involving a direct repression of the core component LYL1 by C/EBPalpha at transcriptional level. We performed a ChIP-seq analysis of the genome-wide occupancy of C/EBPalpha and identifeid a -1 kb C/EBPalpha-binding site in the LYL1 locus that mediate this repression. As LYL1 acts as a linker between the AML1-ETO-E and LMO2-LDB1 parts of AETFC, depletion of LYL1 causes a destabilization of AETFC, which increases susceptibility of the leukemic cells to differentiation. Our results have provided a novel mechanism by which C/EBPalpha can directly destabilize AETFC, and have identified LYL1 as a new therapeutic target for treatment of t(8;21) leukemia.
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| Overall design |
Since the expression of C/EBPalpha in the AML1-ETO-expressing Kasumi-1 cells is very low, we overexpressed an HA-tagged C/EBPalpha in the cells and performed the ChIP-seq with an anti-HA antibody. We also performed RNA-seq analysis of the C/EBPalpha-overexpressing Kasumi-1 cells and the control cells transduced with the MIGR1 vector.
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| Web link |
https://www.nature.com/articles/s41375-019-0398-8
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| Contributor(s) |
Zhang M, Liu N, Zhang Y, Rong B, Xu C, Lan F, Huang Q, Sun X |
| Citation(s) |
30755707 |
| |
| Submission date |
May 18, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Chun-hui Xu |
| E-mail(s) |
xuch@sibs.ac.cn
|
| Organization name |
Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine
|
| Department |
State Key Laboratory of Medical Genomics
|
| Street address |
197 Ruijin Road II
|
| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200025 |
| Country |
China |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA472044 |
| SRA |
SRP148441 |
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