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Status |
Public on Nov 15, 2017 |
Title |
Genome wide mapping of ETV6 binding sites in pre-B leukemic cells |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Background: Genetic alterations in the transcriptional repressor ETV6 are associated with hematological malignancies. Notably, the t(12;21) translocation leading to an ETV6-AML1 fusion gene is the most common genetic alteration found in childhood acute lymphoblastic leukemia. Moreover, most of these patients also lack ETV6 expression, suggesting a tumor suppressor function. Results: To gain insights on ETV6 DNA-binding specificity and genome wide transcriptional regulation capacities, we performed chromatin immunoprecipitation experiments coupled to deep sequencing in a t(12;21)-positive pre-B leukemic cell line. This strategy led to high quality ETV6-bound regions. ETV6 binding is mostly cell type-specific as only few regions are shared with other blood cell subtypes. Peaks localization and motif enrichment analyses revealed a unique binding profile that is associated with the presence of the ETV6-AML1 fusion product. Conclusions: We described the first ETV6 binding map in the t(12;21) background. This study highlighted the complex and unique interplay between ETV6 and ETV6-AML1 and underscored the highly regulated mechanisms of ETV6 binding. ETV6 inactivation observed in this context could induce specific transcriptional changes promoting leukemic transformation.
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Overall design |
Genome wide ETV6 binding sites were identified through chromatin immunoprecipitation sequencing in ETV6-HA transduced Reh cells compared to ETV6 (negative IP control), each in triplicates
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Contributor(s) |
Neveu B, Caron M, Lagacé K, Richer C, Sinnet D |
Citation missing |
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Submission date |
Aug 17, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Daniel Sinnett |
E-mail(s) |
daniel.sinnett@umontreal.ca
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Organization name |
CHU Sainte-Justine
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Street address |
3175 Cote-Sainte-Catherine
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City |
Montreal |
State/province |
Quebec |
ZIP/Postal code |
H3T 1C5 |
Country |
Canada |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (2) |
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Relations |
BioProject |
PRJNA398678 |
SRA |
SRP115657 |