Schick, Sandra and Rendeiro, Andre F. and Runggatscher, Kathrin and Ringler, Anna and Boidol, Bernd and Hinkel, Melanie and Majek, Peter and Vulliard, Loan and Penz, Thomas and Parapatics, Katja and Schmidl, Christian and Menche, Joerg and Boehmelt, Guido and Petronczki, Mark and Mueller, Andre C. and Bock, Christoph and Kubicek, Stefan (2019) Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers. NATURE GENETICS, 51 (9). 1399-+. ISSN 1061-4036, 1546-1718
Full text not available from this repository. (Request a copy)Abstract
Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer-type-specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knockout cell lines deficient for 22 BAF subunits. We observe strong, specific and sometimes discordant alterations dependent on the targeted subunit and show that these explain intracomplex codependencies, including the synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest approaches to therapeutically target BAF-mutant cancers.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHROMATIN-REMODELING COMPLEX; CHIP-SEQ; SWI/SNF; APOPTOSIS; PLK1; ESSENTIALITY; SPECIFICITY; ANNOTATION; ALIGNMENT; ELEMENTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 07:05 |
| Last Modified: | 31 Mar 2020 07:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26357 |
Actions (login required)
 |
View Item |
