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Series GSE52595 Query DataSets for GSE52595
Status Public on Dec 02, 2013
Title Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation (4C-seq)
Organism Mus musculus
Experiment type Other
Summary Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs
Overall design Enhancer usually regulates its targets through physical contact/interaction. In order to study chromosome conformation of Myc locus and potential distal enhancer E1-E5 region in murine AML cells, we utilize the high resolution 4C-seq and analysis pipeline to search cis elements that physical interact with Myc and E1-E5 region through setting up two individual viewpoints in these two regions.
Contributor(s) Shi J, Zepeda-Mendoza CJ, Spector DL, Vakoc CR
Citation(s) 24285714
Submission date Nov 20, 2013
Last update date May 15, 2019
Contact name Christopher R Vakoc
Organization name Cold Spring Harbor Lab
Lab Vakoc Lab
Street address 1 Bungtown Rd
City Cold Spring Harbor
State/province NY
ZIP/Postal code 11724
Country USA
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (6)
GSM1272324 TSS_RN2_1
GSM1272325 TSS_RN2_2
GSM1272326 Enh_RN2_1
This SubSeries is part of SuperSeries:
GSE52279 Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation
BioProject PRJNA229509
SRA SRP033249

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Supplementary file Size Download File type/resource
GSE52595_RAW.tar 1.6 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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