Constanze Breitinger

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Stimulation of transcriptional elongation is a key activity of leukemogenic MLL fusion proteins. Here, we provide evidence that MLL-ENL also inhibits Polycomb-mediated silencing as a prerequisite for efficient transformation. Biochemical studies identified ENL as a scaffold that contacted the elongation machinery as well as the Polycomb repressive complex 1(More)
HOX proteins are widely involved in hematopoietic development. These transcription factors combine a conserved DNA-binding homeobox with a divergent N-terminus that mediates interaction with variable cofactors. The resulting combinatorial diversity is thought to be responsible for mammalian HOX specificity. Contrasting this proposed mechanism for normal HOX(More)
HOX homeobox transcription factors are not only master regulators of segment identity but also instrumental for proper blood formation (reviewed in Argiropoulos and Humphries and Eklund). The physiology of hematopoietic stem and progenitor cells (HSPC) is under the direct control of HOX proteins. In particular, members of the ‘HOX-A’ and ‘HOX-B’ paralog(More)
Mixed-lineage leukemia fusion proteins activate their target genes predominantly by stimulating transcriptional elongation. A core component necessary for this activity is cyclin-dependent kinase 9. Here we explored the effectiveness of small molecules targeting this enzyme as potential therapeutics. A screen of seven compounds with anti-CDK9 activity(More)
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