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Series GSE71777 Query DataSets for GSE71777
Status Public on Jun 12, 2016
Title RNASeq of MV4;11 cell treated with DMSO, I-BET, SGC0946 and combination of I-BET and SGC0946
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Central to the molecular pathogenesis of MLL leukaemia is the abnormal co-optation of members of transcription complexes including disrupter of telomeric silencing 1-like (DOT1L) and bromodomain containing protein 4 (BRD4). Consequently, targeted therapies against DOT1L and BRD4 are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukaemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation we find that native BRD4 and DOT1L exist in largely separate protein complexes. Genetic disruption or small molecule inhibition of BRD4 and DOT1L shows marked synergistic activity against MLL-FP leukaemia cell lines, primary human leukaemia cells and murine leukaemia models. Mechanistically, we find a previously unrecognised functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in close proximity to superenhancers. DOT1L via H3K79me2 facilitates the deposition of histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide novel insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this poor prognostic disease.
Overall design RNASeq of MV4;11 cell treated with DMSO, I-BET, SGC0946 and combination of I-BET and SGC0946 in duplicate
Contributor(s) Dawson M, Gilan O, Lam E
Citation(s) 27294782
Submission date Aug 06, 2015
Last update date May 15, 2019
Contact name Mark Dawson
Organization name Peter MacCallum Cancer Centre
Street address 305 Grattan Street
City Melbourne
State/province VIC
ZIP/Postal code 3000
Country Australia
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (8)
GSM1845147 DMSO Rep 1
GSM1845148 DMSO Rep 2
GSM1845149 I-BET treated Rep 1
This SubSeries is part of SuperSeries:
GSE71780 Functional interdependency of BRD4 and DOT1L in MLL leukaemia
BioProject PRJNA292066
SRA SRP062099

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Supplementary file Size Download File type/resource
GSE71777_RNASeqCPM.txt.gz 491.4 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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