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Status |
Public on May 26, 2015 |
Title |
Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
This study characterizes the genome-side occupancy of AML1, AML1-ETO and the cofactors N-CoR and p300 in leukemics cells (Kasumi-1) to discover novel regulatory mechanisms involving genes bound by the t(8:21) fusion protein AML1-ETO. A significant discovery of our study is the co-localization of AML1-ETO with the N-CoR co-repressor on genomic regions that are primarily distal to the transcriptional start sites (TSSs). These regions exhibit over-representation of the PU.1 motif: PU.1 is a key hematopoietic regulator and member of the ETS family of transcription factors. Functionally, genes co-occupied by AML1-ETO and N-CoR (e.g., TYROBP and LAPTM5) are associated with the leukemic phenotype, as determined by analyses of gene ontology and by the observation that these genes are predominantly up-regulated upon AML1-ETO depletion. To further probe the regulatory context of these leukemic cells, genome-wide enrichment of the transcriptional initiation-associated histone modification H3K4me3 was also measured.
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Overall design |
Genome-wide study of transcription factor-DNA binding for AML1 (RUNX1) and the t(8;21) fusion protien AML1-ETO (RUNX1T1) in the Kasumi-1 leukemia cell line. The genome-wide binding of the disease-related cofactors N-CoR and p300 was assayed, along with enrichments of the H3K4me3 and H3K27me3 histone modifications.
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Contributor(s) |
Whitfield TW, Trombly DJ |
Citation(s) |
25928846 |
Submission date |
Oct 30, 2014 |
Last update date |
Nov 05, 2019 |
Contact name |
Troy W. Whitfield |
Organization name |
University of Massachusetts Medical School
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Street address |
55 Lake Ave. N.
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City |
Worcester |
ZIP/Postal code |
01655 |
Country |
USA |
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Platforms (1) |
GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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Samples (7)
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Relations |
BioProject |
PRJNA265834 |
SRA |
SRP049405 |