Article
Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue-unrestricted enhancers.
Nature structural & molecular biology - 1 Jan 2018
Hodges H Courtney, Stanton Benjamin Z, Cermakova Katerina, Chang Chiung-Ying, Miller Erik L, Kirkland Jacob G, Ku Wai Lim, Veverka Vaclav, Zhao Keji, Crabtree Gerald R
Abstract excerpt
Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes, contributes to a range of malignancies and neurologic disorders. Unfortunately, the effects of SMARCA4 missense mutations have remained uncertain. Here we show that SMARCA4 cancer missense mutations target conserved ATPase surfaces and disrupt the mechanochemical cycle of remodeling. We find that heterozygous expression of mutants alters...
Topics
- Adenosine Triphosphatases
- Animals
- Chromatin
- Chromatin Assembly and Disassembly
- Culture Media
- DNA Helicases
- Enhancer Elements, Genetic
- Epigenomics
- Genes, Dominant
- Genotype