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| Status |
Public on Nov 11, 2014 |
| Title |
TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemias |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Members of the TALE (Three-amino acid loop extension) family of atypical homeodomain-containing transcription factors are prominent downstream effectors of oncogenic fusion proteins generated from translocations involving the mixed lineage leukemia (MLL) gene. A particular well-characterized member of this protein family is MEIS1, which together with HOXA proteins, orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). Although TALE family proteins are mainly described as transcriptional activators TGIF1 (TGF-β induced factor) / TGIF2 are considered as transcriptional repressors. However, as their function in MLL-rearranged AML is largely unknown, we tested the potential importance of TGIF1 in the maintenance of MLL-rearranged AML. We find that expression of TGIF1 in MLL-AF9 transformed cells (MAF9) leads to cell cycle exit and differentiation in vitro and delayed leukemic onset in vivo. In accordance, MLL-rearranged patient blasts display lower levels of TGIF1 and TGIF1 expression in general correlates positively with survival. Mechanistically, we show that TGIF1 interferes with a MEIS1-dependent transcriptional program by associating to MEIS1-bound region in a competitive manner. Collectively, these findings demonstrate that TALE family members can act both positively and negatively on transcriptional programs responsible for the maintenance of MLL-rearranged AML.
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| Overall design |
Examination of TGIF1 and Meis1 binding in MLL-AF9 transformed cells. ChIP-seq was carried out in dublicates
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| Contributor(s) |
Willer A, Porse B |
| Citation(s) |
25349154 |
| Submission date |
Feb 24, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Bo Porse |
| E-mail(s) |
bo.porse@finsenlab.dk
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| Organization name |
Rigshospitalet
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| Department |
Finsen Centre
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| Lab |
Finsen laboratory
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| Street address |
Ole Maaloesvej 5
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| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA239207 |
| SRA |
SRP038866 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE55287_RAW.tar |
2.3 Gb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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