Unknown

Dataset Information

0

The SWI/SNF ATPase BRG1 facilitates multiple pro-tumorigenic gene expression programs in SMARCB1-deficient cancer cells.


ABSTRACT: Malignant rhabdoid tumor (MRT) is driven by the loss of the SNF5 subunit of the SWI/SNF chromatin remodeling complex and then thought to be maintained by residual SWI/SNF (rSWI/SNF) complexes that remain present in the absence of SNF5. rSWI/SNF subunits colocalize extensively on chromatin with the transcription factor MYC, an oncogene identified as a novel driver of MRT. Currently, the role of rSWI/SNF in modulating MYC activity has neither been delineated nor has a direct link between rSWI/SNF and other oncogenes been uncovered. Here, we expose the connection between rSWI/SNF and oncogenic processes using a well-characterized chemical degrader to deplete the SWI/SNF ATPase, BRG1. Using a combination of gene expression and chromatin accessibility assays we show that rSWI/SNF complexes facilitate MYC target gene expression. We also find that rSWI/SNF maintains open chromatin at sites associated with hallmark cancer genes linked to the AP-1 transcription factor, suggesting that AP-1 may drive oncogenesis in MRT. Interestingly, changes in MYC target gene expression are not overtly connected to the chromatin remodeling function of rSWI/SNF, revealing multiple mechanisms used by rSWI/SNF to control transcription. This work provides an understanding of how residual SWI/SNF complexes may converge on multiple oncogenic processes when normal SWI/SNF function is impaired.

SUBMITTER: Moe KC 

PROVIDER: S-EPMC9160003 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

The SWI/SNF ATPase BRG1 facilitates multiple pro-tumorigenic gene expression programs in SMARCB1-deficient cancer cells.

Moe Kylie C KC   Maxwell Jack N JN   Wang Jing J   Jones Cheyenne A CA   Csaki Grace T GT   Florian Andrea C AC   Romer Alexander S AS   Bryant Daniel L DL   Farone Anthony L AL   Liu Qi Q   Tansey William P WP   Weissmiller April M AM  

Oncogenesis 20220601 1


Malignant rhabdoid tumor (MRT) is driven by the loss of the SNF5 subunit of the SWI/SNF chromatin remodeling complex and then thought to be maintained by residual SWI/SNF (rSWI/SNF) complexes that remain present in the absence of SNF5. rSWI/SNF subunits colocalize extensively on chromatin with the transcription factor MYC, an oncogene identified as a novel driver of MRT. Currently, the role of rSWI/SNF in modulating MYC activity has neither been delineated nor has a direct link between rSWI/SNF  ...[more]

Similar Datasets

2022-05-31 | GSE198156 | GEO
| PRJNA813879 | ENA
| S-EPMC1383528 | biostudies-literature
| S-EPMC5235921 | biostudies-literature
| S-EPMC3547967 | biostudies-literature
| S-EPMC10931202 | biostudies-literature
| S-EPMC5740901 | biostudies-literature
| S-EPMC5285474 | biostudies-literature
| S-EPMC10405256 | biostudies-literature
| S-EPMC2665061 | biostudies-literature