The role of BAF (mSWI/SNF) complexes in mammalian neural development

Son, Esther; Crabtree, Robert H.

doi:10.1002/ajmg.c.31416

Cited by 138 publications

(145 citation statements)

References 173 publications

(264 reference statements)

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…The importance of the BAF complex in human brain development has emerged through recent discoveries that mutations in subunits including SMARCA2, SMARCB1, SMARCA4, ARID1A, and ARID1B have all been implicated in ID and related neurobehavioral disorders including Nicolaides-Baraitser syndrome [18], Coffin-Siris syndrome [17], autism [2], and schizophrenia [35]. The high frequency of BAF subunit mutations in neurological disorders underscores the fundamental importance of BAF in the development and function of the central nervous system [36].…”

Section: Resultsmentioning

confidence: 96%

Mutations in ARID2 are associated with intellectual disabilities

Shang

Cho²,

Retterer³

et al. 2015

Neurogenetics

View full text Add to dashboard Cite

The etiology of intellectual disabilities (ID) remains unknown for the majority of patients. Due to reduced reproductive fitness in many individuals with ID, de novo mutations account for a significant portion of severe ID. The ATP-dependent SWI/SNF chromatin modifier has been linked with neurodevelopmental disorders including ID and autism. ARID2 is an intrinsic component of polybromo-associated BAF (PBAF), the SWI/SNF subcomplex. In this study, we used clinical whole exome sequencing (WES) in proband-parent-trios to identify the etiology of ID. We identified four independent, novel, loss of function variants in ARID2 gene in four patients, three of which were confirmed to be de novo. The patients all have ID and share other clinical characteristics including attention deficit hyperactivity disorder, short stature, dysmorphic facial features, and Wormian bones. All four novel variants are predicted to lead to a premature termination with the loss of the two conservative zinc finger motifs. This is the first report of mutations in ARID2 associated with developmental delay and ID.

show abstract

Section: Resultsmentioning

confidence: 96%

Mutations in ARID2 are associated with intellectual disabilities

Shang

Cho²,

Retterer³

et al. 2015

Neurogenetics

View full text Add to dashboard Cite

show abstract

“…Depending on their function, CREs can be divided into functionally different classes, with the proximal promoters, enhancers, insulators and silencers being the most widely studied [6–10]. While other regulatory elements operating in trans- or in cis- , including but not limited to chromatin remodelers, RNA-binding proteins, regulatory RNAs, and cis -regulatory RNA elements also exist and function at the transcriptional or post-transcriptional level [11], the complex sets of interactions among TFs and CREs form the central core of transcriptional regulatory networks (TRNs) (BOX 1) [1]. …”

Section: Cis-regulatory Elements Are Integral Components Of Transcripmentioning

confidence: 99%

“…The BAF (mSWI/SNF) chromatin remodeling complex is involved in regulating the size and thickness of the neocortex [42] and the ability of PAX6 to bind to specific CREs and regulate downstream target genes is modulated by this complex during adult neurogenesis [43]. These studies suggest that epigenetic mechanisms such as chromatin remodeling [11] may play a critical role in the transcriptional regulation of neurogenesis throughout development. In addition, specific non-coding RNAs have been shown to regulate cortical neurogenesis by targeting multiple key TFs [44, 45], providing a regulatory feedback mechanism and another layer of complexity.…”

Section: Transcriptional Regulation Of Neocortical Neurogenesis and Gmentioning

confidence: 99%

From trans to cis: transcriptional regulatory networks in neocortical development

2015

View full text Add to dashboard Cite

Transcriptional mechanisms mediated by the binding of transcription factors to cis-acting regulatory DNA elements play critical roles in directing gene expression. While transcription factors have been extensively studied, less effort has gone towards the identification and functional characterization of cis-regulatory elements and associated epigenetic modulation. However, due to methodological and analytical advances, more comprehensive studies of regulatory elements and mechanisms are now possible. Here we summarize recent progress in integrative analyses of these regulatory components in the development of the cerebral neocortex, the part of the brain involved in cognition and complex behavior. These studies are uncovering not only the underlying transcriptional regulatory networks, but also how these networks are altered across species and in neurological and psychiatric disorders.

show abstract

“…These data suggest that BAF complexes function in normal neural development and that mutations cause autistic disorders. Previously, we identified a neuron-specific BAF complex (nBAF) that regulates neuronal gene expression and is required for neural development (19)(20)(21). The BAF53b subunit of nBAF complexes is required for activity-dependent dendrite growth and learning and memory (19,22).…”

mentioning

confidence: 99%

Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling

Zhang

Cao

Chang

et al. 2016

Molecular and Cellular Biology

View full text Add to dashboard Cite

Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASDassociated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Synapses formed between axons and dendrites connect neurons and generate neural circuits that control brain functions (1). The dysregulation of synapse formation, maturation, or plasticity causes many neurodevelopmental diseases such as autism (2). Autism spectrum disorders (ASDs) are complex diseases characterized by a range of behavior abnormalities and regulated by genetic and epigenetic factors (3-5). In ASDs with various genetic or environmental causes, synaptic dysfunction is a central defect.Many autism risk genes encode transcription factors and epigenetic regulators, which likely function to regulate the expression of synaptic genes (4, 6, 7). A gene network analysis predicted the core subunit of a SWI/SNF-like BRG1-associated factor (BAF) ATP-dependent chromatin remodeling complex, Brg1/SmarcA4, as one of the key nodes in autism pathogenesis (7). BAF complexes containing the ATPase Brg1 or Brm use energy derived from ATP hydrolysis to modulate chromatin structures and regulate transcription (8-10). Mutations in several BAF subunits are the genetic causes of Coffin-Siris syndrome and Nicolaides-Baraitser syndrome with autistic symptoms such as intellectual disability and delayed speech (11-15). In addition, de novo functional mutations of genes encoding several BAF subunits are identified repeatedly in autism patients (7,(16)(17)(18). Mutations in a gene encoding the BAF-associated protein activity-dependent ...

show abstract

The role of BAF (mSWI/SNF) complexes in mammalian neural development

Cited by 138 publications

References 173 publications

Mutations in ARID2 are associated with intellectual disabilities

Mutations in ARID2 are associated with intellectual disabilities

From trans to cis: transcriptional regulatory networks in neocortical development

Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling

Contact Info

Product

Resources

About