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Series GSE244197 Query DataSets for GSE244197
Status Public on Feb 26, 2024
Title CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia (CHIPseq)
Organism Homo sapiens
Experiment type Genome binding/occupancy 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 CHIPseq of BRD4, Pol II, and H3K27ac from CUTLL1 cells treated with control shRNA (CT) and CHMP5 shRNA (KD).
 
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)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM7808516 CUTLL1 BRD4 CT
GSM7808517 CUTLL1 BRD4 KD
GSM7808518 CUTLL1 Pol II CT
This SubSeries is part of SuperSeries:
GSE244200 CHMP5-Mediated Transcriptional Regulation of T-Cell Acute Lymphoblastic Leukemia
Relations
BioProject PRJNA1021645

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE244197_CT2-BRD4_peaks.xls.gz 304.8 Kb (ftp)(http) XLS
GSE244197_CT2-H3k27_peaks.xls.gz 582.4 Kb (ftp)(http) XLS
GSE244197_CT2-RNApol_peaks.xls.gz 31.0 Kb (ftp)(http) XLS
GSE244197_KD2-BRD4_peaks.xls.gz 313.5 Kb (ftp)(http) XLS
GSE244197_KD2-H3k27_peaks.xls.gz 459.1 Kb (ftp)(http) XLS
GSE244197_KD2-RNApol_peaks.xls.gz 27.6 Kb (ftp)(http) XLS
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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