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| Status |
Public on Jul 05, 2022 |
| Title |
A direct comparison between AML1-ETO and ETO2-GLIS2 leukemia fusion proteins reveals distinct transcriptional properties and context-dependent binding and regulation of target genes (RNA-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The ETO-family transcriptional corepressors, including ETO, ETO2 and MTGR1, are all involved in leukemia-causing chromosomal translocations. In every case, an ETO-family corepressor acquires a DNA-binding domain (DBD) to form a typical transcription factor – the DBD binds to target genes, while the ETO moiety contributes essentially to its transcriptional property. A direct comparative study of these “homologous” fusion transcription factors may clarify their similarities and differences in regulating transcription and leukemogenesis. Here, we performed a side-by-side comparison between AML1-ETO and ETO2-GLIS2, the most common fusion proteins in the M2 and M7 subtypes of acute myeloid leukemia, respectively, by inducible expression of them in U937 leukemia cells. We found that, although AML1-ETO and ETO2-GLIS2 can use their own DBDs (i.e., the Runt domain of AML1 and the zinc finger domain of GLIS2) to bind DNA, they actually share a large proportion of genome-wide binding regions dependent on other cooperative transcription factors such as ETS- and CEBP-family proteins. Functionally, AML1-ETO acts as either transcriptional repressor or activator, whereas ETO2-GLIS2 mainly acts as an activator. The repressor-versus-activator functions of AML1-ETO is determined by the abundance of cooperative transcription factors/cofactors on the target genes. Through these mechanisms, AML1-ETO and ETO2-GLIS2 differentially regulate several key transcription factors that are essential for myeloid differentiation. Indeed, AML1-ETO inhibits myeloid differentiation of U937 cells, whereas ETO2-GLIS2 facilitates it. Taken together, this study is the first direct comparative study between AML1-ETO and ETO2-GLIS2 in the same cellular context, and the results provide new insights into the context-dependent transcriptional regulatory mechanisms that may underlie how these seemingly “homologous” fusion transcription factors exert distinct functions to drive different subtypes of leukemia.
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| Overall design |
Comparative gene expression profiling analysis of RNA-seq data for U937-CTR cells and its inducible over-expressed derivatives (U937-AE, U937-EG).
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| Contributor(s) |
Zhang Y, Sun X |
| Citation(s) |
36158200 |
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| Submission date |
Jun 29, 2022 |
| Last update date |
Oct 04, 2022 |
| Contact name |
Yifan Zhang |
| E-mail(s) |
zhangyf57@sjtu.edu.cn
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| Phone |
19121708692
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| Organization name |
Shanghai Institute of Hematology
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| Street address |
Ruijin Hospital
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| City |
Shanghai, China |
| ZIP/Postal code |
200001 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| This SubSeries is part of SuperSeries: |
| GSE207218 |
A direct comparison between AML1-ETO and ETO2-GLIS2 leukemia fusion proteins reveals distinct transcriptional properties and context-dependent binding and regulation of target genes |
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| Relations |
| BioProject |
PRJNA854169 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE207217_RAW.tar |
4.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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