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Series GSE127507 Query DataSets for GSE127507
Status Public on Nov 06, 2019
Title A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia [ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Treatment of cells carrying MLL-rearrangements with VTP-50469 (specific Menin-MLL1 inhibitor) displaces Menin from high molecular weight complexes and chromatin genome-wide. Since VTP-50469 block Menin interaction with MLL1 we tested using chip-seq if treatment with VTP-50469 also displaces MLL1 or MLL-fusions from chromatin. We found that the VTP-50469 treatment displaced MLL-fusions from only a subset of MLL-fusion binding sites. Since DOT1L is associated with MLL-AF9 we then tested if displacement of MLL1 also leads to loss of DOT1L association with chromatin on MLL-AF9 binding sites. We found that DOT1L binds to thousands of genes, treatment with VTP-50469 leads to genome wide loss of DOT1L binding including the same subset of MLL-fusion binding sites.
 
Overall design Using ChIP-seq we examined Menin, MLL1, and DOT1L genome binding sites as well as methylation of lysine 79 on Histone H3 (H3K79me2) in cell lines carrying MLL-rearrangements MOLM13 (MLL-AF9), RS4;11 (MLL-AF4) and ML-2 (MLL-AF6) treated with VTP-50469 (100-330nM) or DMSO for 2-4 days.
 
Contributor(s) Hatton C, Krivtsov A
Citation(s) 31821784
Submission date Feb 28, 2019
Last update date Feb 11, 2020
Contact name Charlie Hatton
E-mail(s) Charles_Hatton@dfci.harvard.edu
Organization name Dana-Farber Cancer Institute
Department Pediatric Oncology
Lab Scott Armstrong/CPCT
Street address 450 Brookline Ave
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (26)
GSM3635674 ML2_ChIP_DOT1L_DMSO_180726_TGGTTGTT
GSM3635675 ML2_ChIP_DOT1L_VTP_180726_TGTACCTT
GSM3635676 ML2_ChIP_MENIN_DMSO_180619_ACAGTGGT
This SubSeries is part of SuperSeries:
GSE127508 A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia
Relations
BioProject PRJNA524887
SRA SRP187096

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
GSE127507_ML2_MOLM13_RS411_ROSE_TSS-associated_DOT1L_MENIN_MLL1_ChIPseq_signal.txt.gz 952.9 Kb (ftp)(http) TXT
GSE127507_RAW.tar 5.6 Gb (http)(custom) TAR (of TDF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record
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