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| Status |
Public on Apr 26, 2018 |
| Title |
The basic helix-loop-helix transcription factor SHARP1 is an oncogenic driver in MLL-AF6 Acute Myelogenous Leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Acute Myeloid Leukemia (AML) with MLL gene rearrangements demonstrate unique gene expression profiles driven by MLL-fusion proteins. Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL rearranged AMLs. SHARP1 is expressed solely in MLL-AF6 AML, and its expression is regulated directly by MLL-AF6 / DOT1L. Suppression of SHARP1 induces robust apoptosis of human MLL-AF6 AML cells. Genetic deletion in mice delays the development of leukemia and attenuated leukemia-initiating potential, while sparing normal hematopoiesis. Mechanistically, SHARP1 binds to transcriptionally active chromatin across the genome and activates genes critical for cell survival as well as key oncogenic targets of MLL-AF6. Our findings demonstrate the unique oncogenic role for SHARP1 in MLL-AF6 AML.
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| Overall design |
ChIP-seq and RNA-seq using ML-2 cells.
ChIP-seq using SHI1 cells.
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| Contributor(s) |
Numata A, Kwok HS, Kawasaki A, Li J, Yang H, Benoukraf T, Kerry J, Ballabio E, Tapia M, Bararia D, Zhou Q, Hong HQ, Deshpande AJ, Welner RS, Delwel R, Taneja R, Milne TA, Tenen DG |
| Citation(s) |
29692408 |
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| Submission date |
Feb 28, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Jia Li |
| Organization name |
Duke-NUS
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| Street address |
8 College Road
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| City |
Singapore |
| ZIP/Postal code |
169857 |
| Country |
Singapore |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (23)
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| Relations |
| BioProject |
PRJNA377303 |
| SRA |
SRP100854 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE95511_RAW.tar |
9.4 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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