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Series GSE244199 Query DataSets for GSE244199
Status Public on Feb 26, 2024
Title CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (Murine RNAseq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design CD45.2 Chmp5f/f CD4cre- (WT) or Chmp5f/f CD4cre+ (KO) bone marrow was transduced with ICN1-NGFR retrovirus and injected into lethally irradiated CD45.1 recipients. After 4 weeks and establishment of T-ALL disease, CD45.2+ NGFR+ cells from the spleen of recipient mice were isolated by FACS and submitted for RNAseq
 
Contributor(s) Umphred-Wilson K, Adoro S, Ratnayake S, Chen Q
Citation(s) 38352301
Submission date Sep 27, 2023
Last update date Feb 26, 2024
Contact name Stanley Adoro
E-mail(s) stanley.adoro@nih.gov
Organization name NCI
Department CCR
Lab EIB
Street address Center Dr
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7808530 ICN1 T-ALL, WT mouse 1
GSM7808531 ICN1 T-ALL, WT mouse 2
GSM7808532 ICN1 T-ALL, WT mouse 3
This SubSeries is part of SuperSeries:
GSE244200 CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia
Relations
BioProject PRJNA1021646

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Supplementary file Size Download File type/resource
GSE244199_murineRNAseq_HTseq_counts.tsv.gz 466.7 Kb (ftp)(http) TSV
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