Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA135857 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:MLL-fusions may induce leukemogenic gene expression programs by recruiting the histone H3K79 methyltransferase to MLL-target promoters. We evaluated gene expression changes after cre-mediated loss of Dot1l in leukemia cells obtained from mice injected with MLL-9 transformed lineage negative bone marrow cells. MLL-AF9 murine leukemia cells carrying two conditional Dot1l alleles were retrovirally transduced with Cre or empty control vector, and gene expression changes were monitored on day 3, 5, and 7 after transduction.
2011-09-12 | E-GEOD-25911 | biostudies-arrayexpress
Project description: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. Chromatin immunoprecipitation followed by Solexa sequencing for H3K4me3, H3K27me3, H3K36me3, H3K79me2 and biotinylated MLL-AF9 in HSC, GMP and LSC.
2011-09-13 | E-GEOD-29130 | biostudies-arrayexpress
Project description: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.
2011-09-13 | GSE29130 | GEO
Project description:Using RNA-seq we examined the transcriptional changes following MLL-AF9 degradation in MLL-AF9-HA-FKPB12 transformed murine (BM2222) and human (HCB1) cells. We also examined transcriptional changes in human MLL-AF9-HA-FKBP12 transformed cells (HCB1) and MOLM13 cells in response to DOT1L inhibition, Menin-MLL inhibition, and the combination of DOT1L and Menin-MLL inhibition. Lastly we assessed gene expression in murine neutrophils isolated directly from mice.
2022-03-03 | GSE173574 | GEO
Project description:The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemias are consistently poor prognosis. One of the most common translocation partners is AF9 (a.k.a. MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites, and present the NMR solution structure of a DOT1L-AF9 complex. We generated structure-guided point mutations with graded effects on recruitment of DOT1L to MLL-AF9. ChIP-Seq analyses of H3K79me2 and H3K79me3 show that graded reduction of the DOT1L interaction with MLL-AF9 results in selective losses in H3K79me2 and me3 marks at MLL-AF9 target genes. Furthermore, the degree of DOT1L recruitment defines the level of MLL-AF9 hematopoietic transformation. Hematopoietic progenitor cells isolated from mouse bone marrow were transduced with retrovirus expressing either wildtype MLL-AF9 (WT), mutants, MLL-AF9 (D544R) and MLL-AF9 (D546R). ChIP-Seq analyses were performed on these wildtype and mutant cells using H3K79me2 and H3K79me3 antibodies. 3 samples corresponding to ChIP-Seq with H3K79me2 antibody: 1) MLL-AF9 (WT) 2) MLL-AF9 (D544R) 3) MLL-AF9 (D546R) 3 Samples Corresponding to ChIP-Seq with H3K79me3 antibody: 4) MLL-AF9 (WT) 5) MLL-AF9 (D544R) 6) MLL-AF9 (D546R)
2015-04-30 | E-GEOD-64365 | biostudies-arrayexpress
Project description:The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemias are consistently poor prognosis. One of the most common translocation partners is AF9 (a.k.a. MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcription. We show that DOT1L has three AF9 binding sites, and present the NMR solution structure of a DOT1L-AF9 complex. We generated structure-guided point mutations with graded effects on recruitment of DOT1L to MLL-AF9. ChIP-Seq analyses of H3K79me2 and H3K79me3 show that graded reduction of the DOT1L interaction with MLL-AF9 results in selective losses in H3K79me2 and me3 marks at MLL-AF9 target genes. Furthermore, the degree of DOT1L recruitment defines the level of MLL-AF9 hematopoietic transformation.
2015-04-30 | GSE64365 | GEO
Project description: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. Examination of histone modifications via ChIP-seq in three human cancer cell lines.
2015-03-30 | E-GEOD-62100 | biostudies-arrayexpress
Project description: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. Examination of gene expression dynamics with and without drug treatment and RNA interference.
2015-03-30 | E-GEOD-61013 | biostudies-arrayexpress
Project description: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. Examination of histone modifications and a chromatin modifier with and without drug treatment and RNA interference.
2015-03-30 | E-GEOD-61016 | biostudies-arrayexpress
Project description: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. Examination of histone modifications and a chromatin modifier with and without drug treatment and RNA interference.
2015-03-30 | E-GEOD-61021 | biostudies-arrayexpress