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| Title / Description | DOT1L Inhibits SIRT1 and SUV39H1-Mediated H3K9 Modification to Maintain Gene Expression (array) |
| Accession | GSE61013 |
| Summary | Methylation of histone 3 on lysine 79 (H3K79) is broadly associated with active gene expression in eukaryotes, and the H3K79 methyltransferase DOT1L is indispensable for specific leukemia subtypes like those with MLL-translocations. We found that suppression of the histone deacetylase SIRT1 rescued MLL-AF9 leukemia cells from their dependence on DOT1L. We show that upon DOT1L inhibition, SIRT1 is required for the acquisition of a repressive chromatin state consistent with facultative heterochromatin around MLL-AF9 target genes in leukemia and other genes possess an H3K79me2(hi), H3K9ac(hi), H3K9me2(low) histone modification profile in normal hematopoietic stem and progenitor cells. |
| Organism | Mus musculus |
| Platform | GPL1261 |
| Normalized | False |
| Parsed SOFT file |
| Differential expression method | Characteristic Direction |
| Cutoff | 500 |
| Gene | SIRT1 |
| Cell | MLLAF9 (Murine leukemic) cells |
| Perturbation | EPZ4777 |
| Disease | 3uM - 21 days |
| Principal Component Analysis | |
| Hierarchical clustering |
| Gene lists | Enrichr | L1000CDS2 | PAEA | |
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