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| Status |
Public on Oct 21, 2020 |
| Title |
Trib1 promotes acute myeloid leukemia progression by modulating transcriptional programs of Hoxa9 [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The pseudokinase Trib1 functions as a myeloid oncogene that recruits E3 ubiquitin ligase COP1 to C/EBP, and interacts with MEK1 to enhance ERK phosphorylation. Close genetic interaction between Trib1 and Hoxa9 has been observed in myeloid leukemogenesis as Trib1 overexpression significantly accelerates Hoxa9-induced leukemia onset. Yet the mechanism how Trib1 functionally modulates Hoxa9 transcription activity is unclear. Here we provide evidence that Trib1 modulates Hoxa9-associated super-enhancers. ChIP-seq analyses identified increased Histone H3K27Ac signals at the super-enhancers such as Erg, Aff3, Spns2 and Coro2 loci, as well as increased mRNA expression of these genes. The modification of super-enhancer activities is mostly achieved by degradation of C/EBP by Trib1 and the MEK/ERK pathway only slightly contributes to the activities. Silencing of Erg abrogates the growth advantage acquired by Trib1 overexpression, indicating that Erg is a critical downstream target of the Trib1/Hoxa9 axis. Moreover, treatment of AML cells with the BRD4 inhibitor JQ1 showed growth inhibition in the Trib1/Erg-dependent manner. Upregulation of ERG by TRIB1 was also observed in human AML cell lines, suggesting that Trib1 is a potential target of Hoxa9-associated AML.
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| Overall design |
Examination of binding sites of 2 transcription factors, Hoxa9 and C/EBPa, and Histone H3K27ac in a single cell line with 2 different conditions
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| Contributor(s) |
Yoshino S, Nakamura T |
| Citation(s) |
32730594 |
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| Submission date |
Nov 13, 2019 |
| Last update date |
Oct 25, 2020 |
| Contact name |
Takuro Nakamura |
| E-mail(s) |
takuro-ind@umin.net
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| Phone |
81-3-3570-0462
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| Organization name |
Japanese Foundation for Cancer Research
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| Department |
The Cancer Institute
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| Lab |
Carcinogenesis
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| Street address |
3-8-31 Ariake, Koto-ku
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| City |
Tokyo |
| ZIP/Postal code |
135-8550 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE140315 |
Trib1 promotes acute myeloid leukemia progression by modulating transcriptional programs of Hoxa9 |
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| Relations |
| BioProject |
PRJNA589286 |
| SRA |
SRP229718 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE140313_RAW.tar |
829.1 Mb |
(http)(custom) |
TAR (of TDF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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