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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition.

ABSTRACT: Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition.

PROVIDER: PRJNA726241 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14360100_1.fastq.gz	Fastqsanger.gz
	SRR14360100_2.fastq.gz	Fastqsanger.gz
	SRR14360101_1.fastq.gz	Fastqsanger.gz
	SRR14360101_2.fastq.gz	Fastqsanger.gz
	SRR14362801_1.fastq.gz	Fastqsanger.gz

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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [ChIP-Seq]

Project description:Using ChIP-seq we examined the occupancy changes of various histone marks and chromatin-bound proteins following accute MLL-AF9 degradation in MLL-AF9-HA-FKPB12 transformed human (HCB1) cells. We also examined occupancy changes of various chromatin-bound proteins 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.

2022-03-03 | GSE173599 | GEO

Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [RNA-Seq]

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.

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Gene expression induced by DOT1L and Menin inhibition in cell line models of leukemia

Project description:Gene expression upon DOT1L inhibition, or Menin inhibition, or a combination of DOT1L and Menin inhibiting agents, was assessed in several MLL-rearranged human cell lines and a mouse model of MLL-AF9 leukemia. The goal of the study was to explore the mechanisms by which the EPZ0004777 and MI-2-2 chemicals collaborate to induce differentiation and cell death in MLL-AF4 and MLL-AF9 leukemias.

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A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia [ChIP-seq]

Project description:Treatment of cells carrying MLL-rearrangements with VTP-50469 (specific Menin-MLL1 inhibitor) displaces Menin from high molecular weight complexes and chromatin genome-wide. Since VTP-50469 block Menin interaction with MLL1 we tested using chip-seq if treatment with VTP-50469 also displaces MLL1 or MLL-fusions from chromatin. We found that the VTP-50469 treatment displaced MLL-fusions from only a subset of MLL-fusion binding sites. Since DOT1L is associated with MLL-AF9 we then tested if displacement of MLL1 also leads to loss of DOT1L association with chromatin on MLL-AF9 binding sites. We found that DOT1L binds to thousands of genes, treatment with VTP-50469 leads to genome wide loss of DOT1L binding including the same subset of MLL-fusion binding sites.

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Project description:We determined the effect of conditional deletion of Menin in MLL-AF9 transformed leukemia cells

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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition [ATAC-seq]

Project description:Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition [ATAC-seq]

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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [SLAM-Seq]

Project description:Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [SLAM-Seq]

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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [RNA-Seq]

Project description:Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [RNA-Seq]

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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition [PRO-seq]

Project description:Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition [PRO-seq]

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Chromatin state changes induced by targeted degradation of MLL-AF9 are phenocopied by combined DOT1L and MENIN inhibition. [ChIP-Seq]

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