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| Status |
Public on Oct 30, 2010 |
| Title |
Differential genomic targeting of the transcription factor TAL1 in alternate hematopoietic lineages |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
TAL1/SCL is a master regulator of hematopoiesis whose expression promotes opposite outcomes depending on the cell type - differentiation in the erythroid lineage or oncogenesis in the T-cell lineage. Here we used a combination of ChIP-sequencing and gene expression profiling to compare the function of TAL1 in normal erythroid and leukemic T-cells. Analysis of the genome-wide binding properties of TAL1 in these two hematopoietic lineages revealed new insight into the mechanism by which transcription factors select their binding sites in alternate lineages. Our study shows limited overlap in the TAL1 binding profile between the two cell types with an unexpected preference for ETS and RUNX motifs adjacent to E-boxes in the T-cell lineage. Furthermore we show that TAL1 interacts with RUNX1 and ETS1, and that these transcription factors are critically required to target TAL1 to genes that modulate T-cell differentiation. Thus, our findings highlight a critical role of the cellular environment in modulating transcription factor binding, and provide insight into the mechanism by which TAL1 inhibits differentiation leading to oncogenesis in the T-cell lineage.
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| Overall design |
Examine TAL1/SCL binding sites in two different cell lineages (i.e. primary human pro-erythroblasts and the Jurkat T-ALL cell line). These records represent the ChIP-seq part of the study. The gene expresssion part is available at GSE20546.
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| Contributor(s) |
Brand M, Yao Z |
| Citation(s) |
21179004, 26944678 |
| Submission date |
Oct 28, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Stephen Tapscott |
| E-mail(s) |
stapscot@fredhutch.org
|
| Organization name |
Fred Hutch Cancer Research Center
|
| Department |
Human Biology
|
| Lab |
Tapscott
|
| Street address |
1100 Fairview N. Ave
|
| City |
Seattle |
| State/province |
WASHINGTON |
| ZIP/Postal code |
98103 |
| Country |
USA |
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| Platforms (1) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
|
| Samples (3) |
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| Relations |
| SRA |
SRP003960 |
| BioProject |
PRJNA131987 |
