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| Status |
Public on Nov 03, 2021 |
| Title |
p300 suppresses the transition of myelodysplastic syndrome to acute myeloid leukemia [DIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
|
| Summary |
The p300 lysine acetyltransferase (KAT) can function as an oncogene or a tumor suppressor in hematologic malignancies. We have identified a tumor suppressor role for p300 in myelodysplastic syndrome (MDS) driven by Tet2 deficiency. Compared to Tet2-null hematopoietic stem and progenitor cells (HSPCs), HSPCs lacking both p300 and Tet2 (double knock out, DKO) displayed enhanced proliferation and impaired differentiation. Consequently, p300Δ/Δ Tet2-/- mice developed acute myeloid leukemia. p300 loss in Tet2-/- HSPCs induced a global epigenomic reprogramming that enhanced leukemogenicity at least in part by increasing expression of Myb, as knock-down of Myb specifically hindered the proliferation of the DKO HSPCs. We show that p300 KAT activity regulates the function of Tet2 null HSPCs, and that augmenting p300 function impairs their unlimited self-renewal. Such a strategy could prove useful in individuals with Tet2 deficient hematopoiesis or MDS.
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| Overall design |
Genomewide 5hmc enrichment was determined for each sample by antibody IP for 5hmc over input using genomic DNA from sorted mouse HSPCs. There were three independent replicates per genotype.
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| Contributor(s) |
Man N, Nimer S |
| Citation(s) |
34622806 |
| |
| Submission date |
Feb 25, 2020 |
| Last update date |
Nov 04, 2021 |
| Contact name |
Stephen Nimer |
| Organization name |
University of Miami
|
| Department |
Sylvester Comprehensive Cancer Center
|
| Street address |
1120 NW 14th ST
|
| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE145878 |
p300 suppresses the transition of myelodysplastic syndrome to acute myeloid leukemia |
|
| Relations |
| BioProject |
PRJNA608641 |
| SRA |
SRP250649 |
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