Omics · study · 2026
Role of Histone H3 Lysine 27 Crotonylation in Gene Transcriptional Repression [c-Myc ChIP-Seq]
Listed in NCBI GEO
Histone lysine acetylation and methylation regulate gene transcription through coordination of chromatin structure and transcriptional activity.
Description
However, our understanding of the role of histones in gene regulation is far from complete, in part due to newly discovered novel histone modifications, whose functions are yet to be uncovered1. Here we report that histone H3 lysine 27 crotonylation (H3K27cr) is selectively recognized by the YEATS domain of GAS41 in association with SIN3a-HDAC1/2 co-repressor complex for gene transcriptional repression.
The GAS41 YEATS domain dimer binds proto-oncogenic transcription factor c-Myc, which recruits GAS41/SIN3a-HDAC1/2 complex to target gene loci in chromatin such as cell cycle inhibitor p21. Transcriptional de-repression of p21, directed by tumor suppressor p53 upon doxorubicin stimulation, entails dissociation of c-Myc/GAS41/SIN3a-HDAC1/2 complex from chromatin, reduced H3K27 crotonylation, and consequentially increased H3K27 acetylation at p21 locus.
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GAS41 knockout or H3K27cr binding depletion with CRISPR/Cas9 results in p21 activation, cell cycle arrest and tumor growth inhibition in mice. Our study explains mechanistically causal effect of GAS41 and c-Myc gene amplification on down-regulation of p21 in human colorectal cancer, and suggests GAS41 as an anti-cancer target. We propose that H3K27 crotonylation represents a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for long-term transcriptional silencing and H3K27 acetylation for transcriptional activation.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347372 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347372 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1529685 ncbi.nlm.nih.gov/bioproject/PRJNA1529685 ↗
project · from NCBI GEO
- PubMed 37311463 pubmed.ncbi.nlm.nih.gov/37311463 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE347372 | 12 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 (75%) |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (73%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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 |