DefinitionThis section has been translated automatically.
The SMARCA4 gene (SMARCA4 stands for: SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4) is a protein-coding gene localized on chromosome 19p13.2. Several transcript variants encoding different isoforms have been found for this gene. An important paralog of this gene is SMARCA2.
General informationThis section has been translated automatically.
The protein encoded by this gene is a member of the SWI/SNF protein family and is similar to the Brahma protein of Drosophila. Members of this family have helicase and ATPase activities and are thought to regulate the transcription of certain genes by altering the chromatin structure around these genes.
The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI, which is required for transcriptional activation of genes normally repressed by chromatin. In addition, this protein can bind BRCA1 and regulate the expression of the tumorigenic protein CD44.
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PathophysiologyThis section has been translated automatically.
The encoded protein is involved in the transcriptional activation and repression of selected genes through chromatin remodeling (alteration of DNA nucleosome topology - Euskirchen G et al. 2012).
SMARCA4 is a component of the SWI/SNF chromatin remodeling complexes that perform important enzymatic activities and alter chromatin structure by ATP-dependent modification of DNA-histone contacts within a nucleosome (Kadoch C et al. 2015).
SMARCA4 is a component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating the calcium-dependent release of a repressor complex and the recruitment of an activator complex.
In quiescent neurons, transcription of the c-FOS promoter is inhibited by SMARCA4-dependent recruitment of a phospho-RB1-HDAC repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, leading to the release of the repressor complex. At the same time, CREBBP is increasingly bound 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 the release of HDAC1 and recruitment of CREBBP. Belongs to the neural precursor-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex).
SMARCA4 is a component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B or SMARCD3/BAF60C (Lange M et al. 2008).
In brown adipose tissue, the encoded protein is involved in the regulation of the expression of thermogenic genes.
Clinical pictureThis section has been translated automatically.
Diseases associated with SMARCA4 include
- Coffin-Siris syndrome 4 (Coffin-Siris syndrome 4: Clinical features: Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and other fingers, varying degrees of developmental or cognitive delay, prominent facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies may include malformations of the heart, gastrointestinal tract, genitourinary system and/or central nervous system. Other common findings include feeding difficulties, slow growth, ophthalmologic abnormalities and hearing impairment (Schrier Vergano S et al. 2024).
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- Rhabdoid tumor predisposition syndrome 2.
