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CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE244200 | GEO | 2024/02/26

REPOSITORIES: GEO

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CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (CHIPseq)

Project description:Oncogene activity rewires cellular transcription to create new transcriptional networks which cancer cells become addicted to through mechanisms that remain unresolved. Using human and mouse models of T-cell acute lymphoblastic leukemia (T-ALL), we identified an essential requirement of the endosomal sorting complex required for transport (ESCRT) protein CHMP5 in enabling the T-ALL transcriptional program. Loss of CHMP5 impaired recruitment of the bromodomain transcriptional coactivator BRD4 to enhancer and super-enhancers which caused RNA polymerase II stalling, resulting in severe downregulation of key pro-leukemogenic genes, including MYC and MYC-target genes. Mechanistically, CHMP5 facilitated BRD4 interaction with the histone acetyl transferase p300 to promote H3K27 acetylation at pro-T-ALL gene regulatory elements. Validating its importance to T-cell leukemogenesis, CHMP5-deficiency mitigated chemoresistance in human T-ALL cells and abrogated T-ALL initiation by oncogenic NOTCH1 in vivo. Collectively, our results uncover an unexpected transcriptional activity of CHMP5 that is essential for T-ALL pathogenesis.

2024-02-26 | GSE244197 | GEO

CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (Murine RNAseq)

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CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia

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CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (CHIPseq)

Project description:CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (CHIPseq)

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Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Project description:CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (Human RNAseq)

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CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (Murine RNAseq)

Project description:CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (Murine RNAseq)

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