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Status |
Public on May 01, 2021 |
Title |
Multiple interactions of the oncoprotein transcription factor MYC with the SWI/SNF chromatin remodeler |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Other
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Summary |
We report that even though SNF5 is the most well-documented SWI/SNF subunit to bind MYC, MYC can use multiple interaction surfaces to interact with SWI/SNF subunits independently of SNF5. In line with this, MYC interacts with the pan-SWI/SNF subunit, BAF155, in multiple SNF5-null malignant rhabdoid tumor (MRT) cell lines and almost all of MYC co-localizes with SWI/SNF subunits on chromatin in MRT. In the MRT cell line, G401, MYC binds to essential genes, although for a purpose that appears distinct from chromatin remodeling, and loss of MYC leads to widespread gene expression changes. Analysis of specific MYC-SWI/SNF target genes in G401 cells reveals that this group of genes are associated with core biological functions linked to protein synthesis and their transcription is directly activated by MYC. These data provide a solid framework in which to interrogate the influence of SWI/SNF on MYC function in cancers in which SWI/SNF or MYC are altered.
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Overall design |
The G401 MRT cell line was engineered to express a lentiviral version of c-MYC containing a N-terminal HA-FKBP12F36V dTAG module and then endogenous MYC was removed by CRISPR-Cas9, resulting in G401 cells expressing MYC that could be removed by addition of dTAG47 molecule. For ChIP-seq and Pro-Seq, engineered G401 cells were treated for 4 hours with dTAG47, or DMSO control. For ATAC-seq and RNA-seq, engineered G401 cells were treated for 24 hours with dTAG47 or DMSO control. For RNA-seq of parental G401 cell lines treated with dTAG47, the experiment was also performed at the 24 hour timepoint.
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Contributor(s) |
Tansey WP, Weissmiller AM, Wang J, Liu Q |
Citation(s) |
33931740 |
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Submission date |
Jan 15, 2021 |
Last update date |
May 05, 2021 |
Contact name |
Jing Wang |
Organization name |
Vanderbilt University Medical Center
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Street address |
2220 Pierce Avenue
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City |
Nashville |
State/province |
TN |
ZIP/Postal code |
37232 |
Country |
USA |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (30)
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Relations |
BioProject |
PRJNA692456 |
SRA |
SRP301949 |