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Title: 
Histone modification profiling of HSC, GMPs and L-GMPS
Measurement Type: 
Histone Modification (ChIP-Seq)
Design Type: 
Case Control Design
Factors: 
Immunoprecipitation Antibody, Cell Type/Cell Line, Organism
Summary: 
Profiling of histone modification, transcription factor binding of MLL-AF9 of HSCs, GMPs and L-GMPs. 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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Citations: 
MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L.
Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, et al.
Cancer Cell. 2011 Jul 12; 20(1):66-78. PMID: 21741597. Abstract
Download: 
Study metadata (ISA-Tab: isa_9260_962717.zip)