Related Experiment Video
Updated: Jun 26, 2026
Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
Published on: May 17, 2016
Antagonistic roles for BRM and BRG1 SWI/SNF complexes in differentiation
Stephen Flowers1, Norman G Nagl, George R Beck
1Department of Orthopaedics, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
Abstract:
The mammalian SWI/SNF chromatin-remodeling complex is essential for the multiple changes in gene expression that occur during differentiation. However, the basis within the complex for specificity in effecting positive versus negative changes in gene expression has only begun to be elucidated. The catalytic core of the complex can be either of two closely related ATPases, BRM or BRG1, with the potential that the choice of alternative subunits is a key determinant of specificity. Short hairpin RNA-mediated depletion of the ATPases was used to explore their respective roles in the well characterized multistage process of osteoblast differentiation. The results reveal an unexpected role for BRM-specific complexes. Instead of impeding differentiation as was seen with BRG1 depletion, depletion of BRM caused accelerated progression to the differentiation phenotype. Multiple tissue-specific differentiation markers, including the tightly regulated late stage marker osteocalcin, become constitutively up-regulated in BRM-depleted cells. Chromatin immunoprecipitation analysis of the osteocalcin promoter as a model for the behavior of the complexes indicates that the promoter is a direct target of both BRM- and BRG1-containing complexes. BRG1 complexes, which are required for activation, are associated with the promoter well before induction, but the concurrent presence of BRM-specific complexes overrides their activation function. BRM-specific complexes are present only on the repressed promoter and are required for association of the co-repressor HDAC1. These findings reveal an unanticipated degree of specialization of function linked with the choice of ATPase and suggest a new paradigm for the roles of the alternative subunits during differentiation.
Insights
The SWI/SNF complex uses BRM or BRG1 ATPases to control gene expression during cell differentiation. BRM depletion accelerates osteoblast differentiation by overriding BRG1
Area of Science:
- Cellular and Molecular Biology
- Epigenetics and Gene Regulation
- Developmental Biology
Background:
- The SWI/SNF chromatin-remodeling complex plays a crucial role in regulating gene expression during cellular differentiation.
- Specificity in gene expression control, particularly distinguishing between positive and negative regulation, is mediated by alternative catalytic subunits within the complex.
- The two ATPases, BRM and BRG1, are key components of the SWI/SNF complex, and their distinct roles in differentiation are under investigation.
Purpose of the Study:
- To investigate the specific roles of the BRM and BRG1 ATPases in the process of osteoblast differentiation.
- To elucidate how the choice of ATPase subunit influences the SWI/SNF complex's function in gene expression.
- To understand the molecular mechanisms by which BRM and BRG1 regulate differentiation markers.
Main Methods:
- Utilized short hairpin RNA (shRNA) to deplete BRM and BRG1 ATPases in cells undergoing osteoblast differentiation.
- Analyzed the expression of multiple tissue-specific differentiation markers, including the late-stage marker osteocalcin.
- Employed chromatin immunoprecipitation (ChIP) to assess the association of BRM- and BRG1-containing complexes with the osteocalcin promoter.
Main Results:
- Depletion of BRG1 impeded osteoblast differentiation, consistent with previous findings.
- Unexpectedly, depletion of BRM accelerated osteoblast differentiation, leading to constitutive upregulation of differentiation markers.
- BRM-specific complexes were found to be associated with the repressed osteocalcin promoter and recruit the co-repressor HDAC1, overriding the activating function of BRG1 complexes.
Conclusions:
- The choice of ATPase subunit (BRM vs. BRG1) confers functional specialization within the mammalian SWI/SNF complex.
- BRM-containing SWI/SNF complexes act as repressors during osteoblast differentiation by inhibiting BRG1's activating function.
- These findings propose a new model for the specialized roles of alternative subunits in regulating differentiation processes.
More Related Videos
Related Concept Videos
01:16TGF - β Signaling Pathway
02:23Master Transcription Regulators
01:23Negative Regulator Molecules
00:57Cellular Differentiation
A zygote is a...
01:28Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
01:21Cell Polarization by Rho Proteins