# Role of Brg1 in Activity-Induced Neuronal Gene Expression and Synaptic Plasticity

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $352,407

## Abstract

Summary
Autism spectrum disorders (ASDs) are complex diseases regulated by genetic and epigenetic factors with
synaptic dysfunction as a center defect. Many ASD-associated genes encode either proteins directly
functioning in synapse or regulators of synaptic genes. By modulating chromatin structure and modifications,
epigenetic regulators function together with transcription factors to direct gene expression in response to
developmental and environmental signals. Recently, the ATP-dependent chromatin remodeling BAF
complexes have been linked to ASDs. Mutations in genes encoding several BAF subunits including the core
ATPase subunit Brg1 cause diseases with autistic symptoms. Recent large-scale genomic studies predicted
BAF core subunit Brg1 (also known as SmarcA4) as one of the key nodes of the ASD gene network. My
previous studies have identified a mammalian neuron specific BAF (nBAF) complex, which plays an essential
role in activity-induced dendritic growth, suggesting a Ca2+ signaling induced chromatin regulation of gene
expression. Recent studies in my lab demonstrated that Brg1 is required for synapse development and
maturation. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-
associated transcription factor MEF2C 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.
Our genomic and proteomic data further suggest that Brg1 is activated by neuronal activities and recruited to
enhancers by both MEF2 and active histone modifications. We hypothesize that Brg1 undergoes activity-
dependent modification changes and coordinates with MEF2 and dynamic epigenetic complexes to specifically
regulate target gene activation and synapse plasticity. In the proposal, we will determine (1) how Brg1 is
recruited by transcription factors and epigenetic marks in response to neuronal activation, (2) how Brg1 is
activated by neuronal activities and regulate target gene transcription, and (3) how Brg1 regulates neuronal
gene expression and synaptic plasticity induced by physiological levels of activities. Our studies will provide
mechanistic insights to the epigenetic regulation of normal neuronal development and impact on neurological
diseases such as ASD.

## Key facts

- **NIH application ID:** 9955369
- **Project number:** 5R01NS096068-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jiang Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,407
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955369

## Citation

> US National Institutes of Health, RePORTER application 9955369, Role of Brg1 in Activity-Induced Neuronal Gene Expression and Synaptic Plasticity (5R01NS096068-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9955369. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*