Authors
Sandra Schick, André F Rendeiro, Kathrin Runggatscher, Anna Ringler, Bernd Boidol, Melanie Hinkel, Peter Májek, Loan Vulliard, Thomas Penz, Katja Parapatics, Christian Schmidl, Jörg Menche, Guido Boehmelt, Mark Petronczki, André C Müller, Christoph Bock, Stefan Kubicek
Publication date
2019/9
Journal
Nature genetics
Volume
51
Issue
9
Pages
1399-1410
Publisher
Nature Publishing Group US
Description
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 …
Total citations
20192020202120222023202411832292915