Global ETD Search
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Showing 1 to 11 of 11 for “"Dot1L"”.
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Mechanistic Insights into Direct Interactions that Mediate the Activity of DOT1L Complex in MLL-Rearranged Leukemia
… these fusion partners are also a part of the DOT1L (disruptor of telomeric silencing 1-like) complex. Aberrant histone H3 Lysine 79 (H3K79) methylation catalyzed by DOT1L was shown to be crucial for the maintenance of MLL-rearranged leukemia. DOT1L is the only known H3K79 methyltransferase, …
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Mechanistic Insights into the Stimulation of Dot1L-Mediated Methylation of Histone H3 by Semisynthetically Ubiquitylated Histone H2b
… disruptor of telomeric silencing-like (Dot1L/KMT4). However, the specific function of uH2B in this crosstalk pathway was not understood, in part due to the challenges associated with isolating or generating homogeneously ubiquitylated H2B for use in biochemical studies. As both …
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The critical role of histone methylation in tumour progression and as anti-cancer targets in neuroblastoma
… for Myc-induced transcriptional activation. DOT1L is the only known histone methyltransferase that catalyses mono-methylation (me), di-methylation (me2) and tri-methylation (me3) at the histone H3K79 position, which have been linked to gene transcriptional activation. JMJD6 is a bi-functional …
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Developmental Origins of Renal Connecting Tubule and Collecting Duct: Role of Aqp2+ Progenitor Cells
… inactivate histone H3 K79 methyltransferase <em>Dot1l</em> (<em>Dot1l<sup>f/f </sup>Aqp2Cre</em>) or activate RFP in Aqp2 lineage cells during development (<em>Aqp2Cre RFP</em>). H3 K79methylation and RFP were used as the tracing markers. Kidney sections were examined by immunofluorescence …
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Implications of a CALM-derived Nuclear Export Signal for CALM-AF10-mediated Leukemogenesis
… cells display global H3K79 hypomethylation. DOT1L, the H3K79 histone methyltransferase, interacts with the OM-LZ domain of AF10, and the AF10 OM-LZ domain has been shown to be necessary and sufficient for CALM-AF10-mediated transformation. These data have suggested a critical role for the …
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Significance of Protein Interactions in Mediating AF9 Function
… ducts by modulating the activity of the Dot1l. It has been shown that Af9-Dot1l promotes H3K79 methylation at specific sites in the ENaCα promoter, which then contributes to its repressed state. A number of reports have described the direct or indirect association of</p><p>the C-terminus …
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The Role of AF9 and AF9-Mediated Protein Interactions in Hematopoiesis and Leukemogenesis
… gene regulatory proteins such as AF4/AF5q31, DOT1L, Pc3/CBX8 and BCoR. These interactions are retained in the oncogenic MLL-AF9 fusion protein, and may be required for leukemic transformation.</p><p>Using bone marrow progenitor cells isolated from conditional Af9 knockout mice, we examined in …
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Using "Designer" Nucleosomes to Study Enzymatic Crosstalk Between Histone Ubiquitylation and Histone Methyltransferases
… and H3 lysine 79 methyltransferase, Dot1L, by investigating the plasticity of ubiquitin position in stimulation of Dot1L methyltransferase activity. Finally, using designer mononucleosomes containing H3 phosphoserine mimetics, crosstalk studies with PRC2 methyltransferase uncovered a …
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Identification of novel genetic vulnerabilities and therapeutic targets in acute myeloid leukaemia using CRISPR dropout screens
… I have validated selected genes using DOT1L, BCL2, MEN1 and many other genes genetic and pharmacological inhibition, and chose candidates for downstream studies. Both the epigenetic modifier KAT2A and SRPK1 as promising KAT2A and spliceosome kinase SRPK1 inhibition demonstrated anti-AML …
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A SEARCH FOR EPIGENETIC VULNERABILITIES OF AML CELLS PERFORMED BY A CDK INHIBITOR¿BASED CRISPR SCREENING
… chromatin-related dependencies such as DOT1L. Extending the screening to AML models where cell cycle manipulation does not result in sensitivity to LSD1 17 inhibition further identified additional context-dependent vulnerabilities unmasked by cell cycle lengthening. Nuclear …
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The Mechanisms of HOXA9-mediated Acute Myeloid Leukaemia Maintenance
… oncogenic AML dependencies, such as BCL2, DOT1L, MLLT1, JMJD1C, KAT7, I identify several other novel downstream HOXA9 targets and susceptibilities in HOXA9-driven AML that can be explored therapeutically. Utilising the acute degradation of HOXA9, I was able to disentangle the …