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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome wide mapping of histone 3 lysine 79 dimethylation in MLL rearranged and control human leukemia cell lines

ABSTRACT: We report the genome wide distribution of H3K79 dimethylation in the human MLL-AF6 rearranged cell line ML2 as well as the human MOLM13 and HL60 cell lines Examination of H3K79 dimethylation in the MLL-AF6 fusion positive human leukemia cell line ML2 and control cell lines MOLM-13 and HL60. The MLL-AF6 positive ML2 cell line (obtained from DSMZ) and the cell lines HL60 and MOLM 13 were grown under standard conditions and 1 million cells were fixed/crosslinked and used for ChIP-seq with H3K79 dimethylation specific antibody Ab3594 (Abcam)

ORGANISM(S): Homo sapiens

SUBMITTER: Amit Sinha

PROVIDER: E-GEOD-43063 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l.

Deshpande Aniruddha J AJ Chen Liying L Fazio Maurizio M Sinha Amit U AU Bernt Kathrin M KM Bernt Kathrin M KM Banka Deepti D Dias Stuart S Chang Jenny J Olhava Edward J EJ Daigle Scott R SR Richon Victoria M VM Pollock Roy M RM Armstrong Scott A SA

Blood 20130129 13

The t(6;11)(q27;q23) is a recurrent chromosomal rearrangement that encodes the MLLAF6 fusion oncoprotein and is observed in patients with diverse hematologic malignancies. The presence of the t(6;11)(q27;q23) has been linked to poor overall survival in patients with AML. In this study, we demonstrate that MLL-AF6 requires continued activity of the histone-methyltransferase DOT1L to maintain expression of the MLL-AF6-driven oncogenic gene-expression program. Using gene-expression analysis and gen ...[more]

PMID: 23361907

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Genome wide mapping of histone 3 lysine 79 dimethylation in MLL-AF6 murine leukemias

Project description:We report the genome wide distribution of H3K79 dimethylation in mouse MLL-AF6 positive leukemias to assess whether this epigenetic mark drives MLL-target gene expression. Examination of H3K79 dimethylation in bone marrow cells from sacrificed terminally ill MLL-AF6 positive leukemic mice. The retroviral MSCV-IRES-neo-MLL-AF6 construct was transduced into mouse bone marrow lineage negative Kit +, Sca + (LSK) cells and these cells were injected after G418 selection into irradiated syngenic mice to establish MLL-AF6 positive leukemias.

2013-04-03 | E-GEOD-43062 | biostudies-arrayexpress

Genome wide mapping of histone 3 lysine 79 dimethylation in MLL rearranged and control human leukemia cell lines

Project description:We report the genome wide distribution of H3K79 dimethylation in the human MLL-AF6 rearranged cell line ML2 as well as the human MOLM13 and HL60 cell lines

2013-04-03 | GSE43063 | GEO

Genome wide mapping of histone 3 lysine 79 dimethylation in MLL-AF6 murine leukemias

Project description:We report the genome wide distribution of H3K79 dimethylation in mouse MLL-AF6 positive leukemias to assess whether this epigenetic mark drives MLL-target gene expression.

2013-04-03 | GSE43062 | GEO

Chromatin immunoprecipitation in dot1 deletion and G1 or G2 arrested yeast cells to identify methylation patterns

Project description:To define the molecular regulators required for differential pattern of H3K79 methylation by Dot1, we performed a GPS screen and discovered that the components of the cell cycle-regulated SBF complex were required for normal levels of H3K79 di- but not trimethylation. Genome-wide mapping revealed that H3K79 di- and trimethylation to present a mutually exclusive pattern on chromatin with M/G1 cell-cycle-regulated genes significantly enriched for H3K79 dimethylation. Since H3K79 trimethylation requires prior monoubiquitination of H2B, we performed genome-wide profiling of H2BK123 monoubiquitination and showed that H2BK123 monoubiquitination is excluded from cell cycle regulated genes and sites containing H3K79me2 but not from H3K79me3 containing regions. A genome-wide screen for factors responsible for the establishment/removal of H3K79 dimethylation resulted in the identification of several genes including NRM1 and WHI3, which both impact the transcription by the SBF, and MBF complexes, further linking the regulation of H3K79's methylation status to the cell cycle.

2009-10-19 | E-MEXP-2273 | biostudies-arrayexpress

Epigenetic profiling of hematopoietic stem cells and leukemia stem cells

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

Expression Profiling of Mixed Lineage Leukemia Cells Treated with a Potent Small-Molecule DOT1L Inhibitor

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2011-07-11 | E-GEOD-29828 | biostudies-arrayexpress

Expression Profiling of Mixed Lineage Leukemia Cells Treated with a Potent Small-Molecule DOT1L Inhibitor

2011-07-11 | GSE29828 | GEO

Genome-wide analysis of H3K79 dimethylation in MLL-AF4 leukemic bone marrow

Project description:We created a mouse model where conditional expression of physiologic levels of an Mll-AF4 fusion oncogene induces development of acute lymphoblastic (ALL) or acute myeloid leukemias (AML). ChIP-chip analysis demonstrated increased histone H3 Lysine 79 (H3K79) dimethylation that correlated with Mll-AF4 associated gene expression profiles in murine ALLs, and in human MLL-rearranged leukemias. In addition, human MLL-rearranged ALLs can be distinguished from other ALLs by their genome-wide H3K79 methylation profiles. Keywords: Cell type comparison

2008-11-04 | GSE12362 | GEO

Genome-wide analysis of H3K79 dimethylation in normal and MLL-AF4 leukemic pre-B cells

2008-11-04 | GSE12361 | GEO

Genome-wide analysis of H3K79 methylation in CD34+ CD19+ cells from normal marrow, MLL-rearranged or MLL-germline ALL

2008-11-04 | GSE12360 | GEO