Omics · study · 2026
Kaiso engages with non-canonical binding motifs to regulate DNA damage responses in breast cancer
Listed in NCBI GEO
In breast cancer, nuclear localization of Kaiso (ZBTB33), a bimodal DNA binding factor, is a hallmark of high grade ductal-type carcinomas, especially in estrogen receptor negative disease.
Description
Regulation of gene expression by Kaiso is orchestrated via its engagement to distinct Kaiso binding sequence (KBS) motifs that either be canonical (cKBS; TCCTGCNA) or CG-containing palindromic KBS (CG-KBS; TCTCGCGAGA), depending on context.
While clinical connection of Kaiso to breast cancer exists, it remains unclear how Kaiso controls bi-modal canonical versus noncanonical transcriptional modulation. Here, we have combined Kaiso-specific chromatin immunoprecipitation (ChIP) and Kaiso-Dam methyltransferase identification (Dam-ID) approaches to map genomic Kaiso binding sites in breast cancer cells. We find that Kaiso mostly occupies the non-canonical CG-KBS sites in transcriptionally active and hypo-methylated (H3K4me3 and H3K27Ac enriched) promoter regions.
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Noncanonical CG-KBS targets are actively transcribed and linked to fast biological processes such as metabolism, cell cycle regulation and DNA damage repair. Functionally, we show that Kaiso expression is essential to prevent DNA damage in breast cancer cells. Loss of Kaiso leads to reduced levels of DNA damage response gene expression.
Treatment with the chemotherapeutic agent cisplatin leads to overt accumulation of DNA damage in cells devoid of Kaiso. Our data thus favor a model in which Kaiso promotes fast transcriptional activation of key cellular processes in cancer cells through binding of its non-canonical consensus site.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309273 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309273 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1335068 ncbi.nlm.nih.gov/bioproject/PRJNA1335068 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE309273 | 14 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[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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:10090 | 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 |