Omics · study · 2026
D-lactate derived from bacteria drives lysine D-lactylation to modulate transcription in liver cells
Listed in NCBI GEO
Emerging evidence suggests that accumulated D-lactate (D-la) induces diverse effects in human intestinal injury diseases.
Description
However, the regulatory mechanism remain elusive. Here, we discover the lysine D-lactylation (D-Kla) induced by D-la and reveal the molecular mechanism underlying D-la-driven D-Kla for transcription regulation.
We first discovered D-Kla in HepG2 cells stimulated by D-la from E. coli secretions. Next, we validated the existence of D-la-driven D-Kla by four approaches, especially including metabolic labelling experiments. Additionally, we uncover that SCOT1 catalyzes the transformation of D-la to D-lactyl-CoA, serving as a key donor for D-Kla.
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Furthermore, we identify the D-Kla landscape with 2895 sites by proteomics analysis and 34 histone D-Kla sites activated by D-la and further indicate the regulation of H3K18-Dla in transcription by CUT&Tag and RNA-seq assays. Finally, we show the effect of D-Kla on inhibiting the hepatocellular carcinoma cells proliferation. In summary, we uncover the D-la-driven D-Kla and reveal a D-Kla-mediated transcription regulation for tumor suppression, providing new insight into the protein modifications induced by microbiota secretions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE269nnn/GSE269963 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269963 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1124506 ncbi.nlm.nih.gov/bioproject/PRJNA1124506 ↗
project · 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% · Mass spectrometry 65% · RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE269963 | 15 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[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |