Molecular and Cellular Biochemistry

, Volume 461, Issue 1–2, pp 171–182 | Cite as

The ATPase BRG1/SMARCA4 is a protein interaction platform that recruits BAF subunits and the transcriptional repressor REST/NRSF in neural progenitor cells

  • Sakthidasan Jayaprakash
  • Srdja Drakulic
  • Zongpei Zhao
  • Bjoern Sander
  • Monika M. GolasEmail author


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.


BRG1/SMARCA4 REST/NRSF BAF SWI/SNF Protein–protein interaction Neural progenitor cells 



Amino acid


Brahma/Brahma-related gene 1-associated factor


Brahma-related gene 1




Base pair


Cytoplasmic extract


REST corepressor


Fetal bovine serum


High mobility group


Isopropyl β-d-1-thiogalactopyranoside




Lysogeny broth


Nuclear extract


Neural progenitor cells


Neuron-restrictive silencer factor


Polyacrylamide gel electrophoresis


Phenyl methane sulfonyl fluoride




Repressor element 1


Repressor element 1 silencing transcription factor


Swi3, Ada2, N-Cor, TFIIIB


Switch independent 3


Switch/sucrose non-fermentable


Sodium dodecyl sulfate






Yellow fluorescent protein


Zinc finger



We wish to thank Juan Yuan for RNA extraction. We are grateful to Golshah Ayoubi and Susanne N. Stubbe for technical assistance, and acknowledge access to the laboratory facilities at the Danish Neuroscience Center House, Aarhus. This work has been supported by the Lundbeck Foundation’s Fellowship program, the Sapere Aude Program of the Danish Council for Independent Research, the Danish Cancer Society, the Carlsberg Foundation, the A.P. Møller Foundation for the Advancement of Medical Sciences, the Fabrikant Einar Willumsens Mindelegat and the Helga og Peter Kornings Fond to M.M.G.

Author contributions

MMG designed the study; all authors performed experiments; SJ, BS, and MMG analyzed and interpreted data; MMG wrote the manuscript; SJ, SD, and BS contributed to the manuscript; and all authors approved the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest related to this study.

Supplementary material

11010_2019_3600_MOESM1_ESM.pdf (83 kb)
Supplementary material 1 (PDF 84 kb)


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Authors and Affiliations

  1. 1.Department of BiomedicineAarhus UniversityAarhus CDenmark
  2. 2.Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus UniversityAarhus CDenmark
  3. 3.Institute of PathologyHannover Medical SchoolHannoverGermany
  4. 4.Department of Human GeneticsHannover Medical SchoolHannoverGermany

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