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Epigenetic profiling of hematopoietic stem cells and leukemia stem cells

GSE29130 Mus musculus; Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 15 samples Submitted 2011/09/13 Platform GPL11002Platform GPL10999Platform GPL13112
Summary
The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been implicated in the development of leukemias bearing translocations that involve the Mixed Lineage Leukemia (MLL) gene. We identified the MLL-fusion targets in a murine MLL-AF9 leukemia model, and conducted epigenetic profiling for H3K79me2, H3K4me3, H3K27me3 and H3K36me3. Histone methylation patterns are highly abnormal on MLL-AF9 fusion target loci, defining a distinct epigenetic lesion involving H3K79. Conditional inactivation of Dot1l leads to specific down-regulation of direct MLL-AF9 targets and an MLL-translocation associated gene expression signature, while global transcription levels remain largely unaffected. This correlated with a greater sensitivity of leukemic blasts towards loss of Dot1l compared to normal hematopoietic cells. Development of in vivo leukemia was absolutely dependent on Dot1l.
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Also filed as BioProject PRJNA140445 and SRA study SRP006724. Searching any of these in the dataset finder brings you back here.

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