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Series GSE186695 Query DataSets for GSE186695
Status Public on Nov 16, 2022
Title A molecular switch between mammalian MLL complexes dictates response to Menin-MLL inhibition [ChIP-seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary The chromatin adaptor Menin interacts with oncogenic fusion proteins encoded by MLL1-rearrangements (MLL1-r), and small molecules that disrupt these associations are currently in clinical trials for the treatment of leukemia. Here, we delineate a molecular switch between the MLL1-Menin and MLL3/4-UTX chromatin modifying complexes that dictates response to Menin-MLL inhibitors. We show that Menin safeguards leukemia cell fitness by impeding binding of the histone demethylase UTX at a subset of non-canonical target gene promoters. Disrupting the interaction between Menin and MLL1 leads to UTX-dependent transcriptional activation of genes with tumor suppressive function. We show that this epigenetic mechanism is operative in murine and human models of AML, and clinical responses to Menin-MLL inhibition in primary human leukemia are accompanied by induction of tumor suppressive gene expression at Menin-UTX targets. These findings shed light on the context-dependent and often antagonistic roles that chromatin regulators exhibit in development and disease and provide mechanistic insight for rational design of targeted epigenetic therapies.
Overall design ChIP-Seq for Menin, UTX, MLL1, MLL3/4 and various histone post-translational modifications in mouse and human leukemia cells and fibroblasts.
Contributor(s) Soto-Feliciano YM, Sánchez-Rivera FJ, Perner F, Armstrong SA, Lowe SW, Allis CD
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Submission date Oct 27, 2021
Last update date Nov 19, 2022
Contact name Douglas Barrows
Phone 7749940981
Organization name Rockefeller University
Street address 1230 York Ave
City New York
State/province NY
ZIP/Postal code 10065
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (30)
GSM5659039 Input_Menin_ChIP_WT-MA9_DMSO
GSM5659040 Menin_ChIP_WT-MA9_DMSO
GSM5659041 Menin_ChIP_WT-MA9_MI-503
This SubSeries is part of SuperSeries:
GSE186711 A molecular switch between mammalian MLL complexes dictates response to Menin-MLL inhibition
BioProject PRJNA775615
SRA SRP343461

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Supplementary file Size Download File type/resource
GSE186695_RAW.tar 7.0 Gb (http)(custom) TAR (of BW, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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