Excel · study · 2026
Cognitive and Synaptic Impairment Induced by Deficiency of Autism Risk Gene Smarcc2 and its Rescue by Histone Deacetylase Inhibition
Listed in NCBI GEO
SMARCC2, which encodes BAF170, a core subunit of chromatin remodeling BAF complex, is one of the top-ranking risk genes for autism spectrum disorder (ASD).
Description
However, the mechanisms linking SMARCC2 haploinsufficiency to ASD remain poorly understood. SMARCC2 binds to many other ASD risk genes involved in transcriptional regulation.
Knockdown (KD) of Smarcc2 in prefrontal cortex (PFC) of adolescent mice led to impaired working memory, with largely intact social and anxiety-like behaviors. Genome-wide RNA-seq analysis revealed that the downregulated genes by Smarcc2 KD were enriched in synaptic transmission. Significant reduction of GABA and glutamate-related genes was also found in PFC of Smarcc2-deficient mice by qPCR profiling.
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In parallel, electrophysiological recordings uncovered the significant impairment of GABAergic and glutamatergic synaptic currents in PFC pyramidal neurons by Smarcc2 KD. Smarcc2 binds to HDAC2, and Smarcc2 KD reduced global histone acetylation and H3K9ac enrichment at synaptic gene Slc1a3 (EAAT1), Slc6a1 (GAT1), and Slc32a1 (VGAT) promoters. Treatment of Smarcc2-deficient mice with romidepsin, a class I histone deacetylase (HDAC) inhibitor, restored H3K9ac level, working memory and synaptic gene expression.
These findings highlight the critical role of Smarcc2 in regulating cognitive and synaptic function, suggesting that targeting HDAC could alleviate deficits in Smarcc2-associated neurodevelopmental disorders.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327210 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327210 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1449491 ncbi.nlm.nih.gov/bioproject/PRJNA1449491 ↗
project · from NCBI GEO
- PubMed 42649243 pubmed.ncbi.nlm.nih.gov/42649243 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE327210 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |