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Series GSE82117 Query DataSets for GSE82117
Status Public on Feb 23, 2017
Title Transcription control by the ENL YEATS domain in acute leukemia [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Recurrent chromosomal translocations involving the mixed lineage leukemia gene (MLL) give rise to highly aggressive acute leukemia associated with poor clinical outcomes. The preferential involvement of chromatin-associated factors in MLL rearrangements belies a dependency on transcriptional control. To identify new targets for therapeutic development in MLL, we performed a genome-scale CRISPR-Cas9 knockout screen in MLL-AF4 leukemia. Among validated targets, we identified the transcriptional regulator, ENL, as an unrecognized dependency particularly indispensable for proliferation. To explain the mechanistic role for ENL in leukemia pathogenesis and the dynamic role in transcription control, we pursued a chemical genetic strategy utilizing targeted protein degradation. ENL loss suppresses transcription initiation and elongation genome-wide, with pronounced effects at genes featuring disproportionate ENL load. Importantly, ENL-dependent leukemic growth was contingent upon an intact YEATS epigenomic reader domain. These findings reveal a novel dependency in acute leukemia and a first mechanistic rationale for disrupting YEATS domains in disease.
Overall design RNA-seq in MV4;11 (Cas9; ENL-FKBP(F36V); ENL -/-) cells with dTAG-13 and EPZ-5676 treatment
Contributor(s) Erb MA, Bradner JE
Citation(s) 28241139
Submission date Jun 01, 2016
Last update date May 15, 2019
Contact name James Bradner
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Bradner Lab
Street address 450 Brookline
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (18)
GSM2183713 mv411_DMSO_24h_r1
GSM2183714 mv411_DMSO_24h_r2
GSM2183715 mv411_DMSO_24h_r3
This SubSeries is part of SuperSeries:
GSE82118 Transcription control by the ENL YEATS domain in acute leukemia
BioProject PRJNA324086
SRA SRP075966

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Supplementary file Size Download File type/resource
GSE82117_ENL_all_fpkm_exprs_norm.txt.gz 2.8 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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