Excel · study · 2026
BRD9 Reads Lactate-Induced H3K18 Lactylation to Drive Oncogenic Chromatin Remodeling in Hepatocellular Carcinoma
Listed in NCBI GEO
Histone lactylation bridges glycolytic metabolism to oncogenic transcription, but its mechanistic readers remain poorly defined.
Description
Here, we identify bromodomain-containing protein 9 (BRD9) as a lactyl-lysine reader that links lactate-driven H3K18 lactylation (H3K18la) to chromatin remodeling in hepatocellular carcinoma (HCC). Clinically, elevated H3K18la levels correlate with poor HCC prognosis.
Structural (NMR) and biophysical analyses demonstrate BRD9’s bromodomain engages H3K18la through its acetyl-lysine pocket with weak, transient affinity, distinct from stable H3K18ac binding, enabling lactate-dependent chromatin interactions. Multi-omics profiling reveals H3K18la recruits BRD9 and the non-canonical BRG1-associated factor (ncBAF) complex to active enhancers and promoters, promoting chromatin accessibility and oncogenic transcription (SPARC, TMEM64, ANGEL1, SCARB1).
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Glycolytic inhibition or BRD9 targeting displaces BRD9 from chromatin, suppresses oncogenes, and impairs HCC proliferation. p300 or HDAC inhibition attenuates H3K18la-driven oncogenic transcription and tumor viability. Our findings establish BRD9 as a metabolic-epigenetic mediator that translates glycolytic flux into chromatin remodeling, offering actionable therapeutic targets for HCC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314155 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314155 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1390174 ncbi.nlm.nih.gov/bioproject/PRJNA1390174 ↗
project · from NCBI GEO
- PubMed 41792243 pubmed.ncbi.nlm.nih.gov/41792243 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE314155 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| 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 |