The ATPase BRG1/SMARCA4 is a protein interaction platform that recruits BAF subunits and the transcriptional repressor REST/NRSF in neural progenitor cells
Copyright policy )The ATPase BRG1/SMARCA4 is a protein interaction platform that recruits BAF subunits and the transcriptional repressor REST/NRSF in neural progenitor cells
The BAF complex (SWI/SNF) is an ATP-dependent chromatin remodeler that adapts the structural organization of the chromatin. Despite a growing understanding of the composition of BAF in different cell types, the interaction network within the BAF complex is poorly understood. Here, we characterized an isoform of the BRG1/SMARCA4 ATPase expressed in human neural progenitor cells. By electron microscopy and image processing, the neural BRG1/SMARCA4 shows an elongated globular structure, which provides a considerably larger surface than anticipated. We show that neural BRG1/SMARCA4 binds to BAF57/SMARCE1 and BAF60A/SMARCD1, two further components of BAF. Moreover, we demonstrate an interaction between the neural BRG1/SMARCA4 isoform and the central neurodevelopmental transcriptional repressor REST/NRSF. Our results provide insights into the assembly of a central transcriptional repressor complex, link the structure of the neural BRG1/SMARCA4 to its role as a protein-protein interaction platform and suggest BRG1/SMARCA4 as a key determinant that directs the BAF complex to specific DNA sites by interacting with transcription factors and regulators.
- Aarhus University Denmark
- Ludwig-Maximilians-Universität München Germany
- Pathologisches Institut Germany
- Universität Augsburg Germany
- Hannover Medical School Germany
Chromosomal Proteins, Non-Histone, DNA Helicases, Nuclear Proteins, BRG1/SMARCA4, Models, Biological, REST/NRSF, Cell Line, Protein–protein interaction, SWI/SNF, DNA-Binding Proteins, Repressor Proteins, Protein Subunits, Neural Stem Cells, Protein Domains, Humans, Protein Isoforms, BAF, Neural progenitor cells, Amino Acid Sequence, Protein Binding, Transcription Factors
Chromosomal Proteins, Non-Histone, DNA Helicases, Nuclear Proteins, BRG1/SMARCA4, Models, Biological, REST/NRSF, Cell Line, Protein–protein interaction, SWI/SNF, DNA-Binding Proteins, Repressor Proteins, Protein Subunits, Neural Stem Cells, Protein Domains, Humans, Protein Isoforms, BAF, Neural progenitor cells, Amino Acid Sequence, Protein Binding, Transcription Factors
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