The Function of SMARCA4
Transcriptional coactivator cooperating with nuclear hormone receptors to potentiate transcriptional activation. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. SMARCA4/BAF190A may promote neural stem cell self-renewal/proliferation by enhancing Notch-dependent proliferative signals, while concurrently making the neural stem cell insensitive to SHH-dependent differentiating cues (By similarity). Acts as a corepressor of ZEB1 to regulate E-cadherin transcription and is required for induction of epithelial-mesenchymal transition (EMT) by ZEB1.
Protein names
Recommended name:
Transcription activator BRG1Short name:
BAF190AAlternative name(s):
ATP-dependent helicase SMARCA4BRG1-associated factor 190A
Mitotic growth and transcription activator
Protein BRG-1
Protein brahma homolog 1
SNF2-beta
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4
- RS1122608 (SMARCA4) ??
- RS112374545 (SMARCA4) ??
- RS11668477 (SMARCA4) ??
- RS11669133 (SMARCA4) ??
- RS1529729 (SMARCA4) ??
- RS17249141 (SMARCA4) ??
- RS55791371 (SMARCA4) ??
- RS56289821 (SMARCA4) ??
- RS8099996 (SMARCA4) ??
To see your genotype, you should be logged in and have a file with your genotype uploaded.
Top Gene-Substance Interactions
SMARCA4 Interacts with These Diseases
Disease | Score |
Substances That Increase SMARCA4
Substances | Interaction | Organism | Category |
Substances That Decrease SMARCA4
Substances | Interaction | Organism | Category |
Advanced Summary
Coffin-Siris syndrome At least six mutations in the SMARCA4 gene can cause Coffin-Siris syndrome. This condition is characterized by delayed development, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features that are described as coarse. The SMARCA4 gene mutations involved in Coffin-Siris syndrome change single protein building blocks (amino acids) in or remove an amino acid from the BRG1 protein. Although it is unclear how these changes affect SWI/SNF complexes, researchers suggest that SMARCA4 gene mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts several cellular processes, which could explain the diverse signs and symptoms of Coffin-Siris syndrome. People with Coffin-Siris syndrome do not appear to have an increased risk of cancer (see below). cancers Mutations in the SMARCA4 gene have been found in certain types of cancer, particularly lung cancer. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. The mechanism by which mutations in the SMARCA4 gene contribute to lung cancer is unknown, although it is thought that changes in SWI/SNF complexes are involved. These changes may impair normal cell differentiation, which leads to the overgrowth of certain cell types, causing cancer. Alternatively, abnormal SWI/SNF complexes may disrupt the regulation of genes that help control the growth and division of cells, which leads to cancer. It is likely that other genetic changes in addition to SMARCA4 gene mutations are necessary for cancer development.
The SMARCA4 gene provides instructions for making a protein called BRG1, which forms one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly DNA is packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is lower than when DNA is loosely packed. Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells. The BRG1 protein and other SWI/SNF subunits are thought to act as tumor suppressors, which keep cells from growing and dividing too rapidly or in an uncontrolled way. The BRG1 protein uses a molecule called ATP, which provides energy for chromatin remodeling, although the exact mechanism of remodeling is unclear.
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
---|
Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
---|
Technical
The following transcription factors affect gene expression:
Tissue specificity:
Colocalizes with ZEB1 in E-cadherin-negative cells from established lines, and stroma of normal colon as well as in de-differentiated epithelial cells at the invasion front of colorectal carcinomas (at protein level).
Gene Pathways:
Molecular Function:
- Androgen Receptor Binding
- Atp Binding
- Dna-Dependent Atpase Activity
- Dna Polymerase Binding
- Helicase Activity
- Lysine-Acetylated Histone Binding
- P53 Binding
- Protein N-Terminus Binding
- Rna Polymerase I Core Element Sequence-Specific Dna Binding
- Rna Polymerase Ii Transcription Coactivator Activity
- Tat Protein Binding
- Transcription Coactivator Activity
- Transcription Corepressor Activity
- Transcription Factor Binding
- Chromatin Binding
Biological Processes:
- Atp-Dependent Chromatin Remodeling
- Beta-Catenin-Tcf Complex Assembly
- Covalent Chromatin Modification
- Chromatin Remodeling
- Negative Regulation Of Androgen Receptor Signaling Pathway
- Negative Regulation Of Cell Growth
- Negative Regulation Of G1/S Transition Of Mitotic Cell Cycle
- Negative Regulation Of Transcription, Dna-Templated
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter During Mitotic Cell Cycle
- Nervous System Development
- Neural Retina Development
- Nucleosome Disassembly
- Positive Regulation By Host Of Viral Transcription
- Positive Regulation Of Glucose Mediated Signaling Pathway
- Positive Regulation Of Pri-Mirna Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
- Positive Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Transcription Of Nuclear Large Rrna Transcript From Rna Polymerase I Promoter
- Positive Regulation Of Wnt Signaling Pathway
- Regulation Of Transcription From Rna Polymerase Ii Promoter
- Spermatid Development