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Series GSE55287 Query DataSets for GSE55287
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
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.
Overall design Examination of TGIF1 and Meis1 binding in MLL-AF9 transformed cells. ChIP-seq was carried out in dublicates
Contributor(s) Willer A, Porse B
Citation(s) 25349154
Submission date Feb 24, 2014
Last update date May 15, 2019
Contact name Bo Porse
Organization name Rigshospitalet
Department Finsen Centre
Lab Finsen laboratory
Street address Ole Maaloesvej 5
City Copenhagen
ZIP/Postal code 2200
Country Denmark
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (9)
GSM1333557 TGIF1_EtOH_Rep1
GSM1333558 TGIF1_EtOH_Rep2
GSM1333559 TGIF1_4OHT_Rep1
BioProject PRJNA239207
SRA SRP038866

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Supplementary file Size Download File type/resource
GSE55287_RAW.tar 2.3 Gb (http)(custom) TAR (of BW, TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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