ZNF296 drives immune evasion in epithelial cancer cells [ATAC-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE283057 | GEO | 2025/09/06
REPOSITORIES: GEO
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Project description:Using a genome-wide CRISPR activation screen, we identified ZNF296, a transcription factor prominently expressed in epithelial cancers, as a key regulator of tumor resistance to NK cell-mediated cytotoxicity. To systematically investigate the mechanisms by which ZNF296 suppresses NK cell-mediated killing, RNA-seq analysis was performed on A549 cells overexpressing ZNF296 (ZNF296-OE), and 4T1 cells with knockdown of its murine homolog Zfp296 (Zfp296KD). By analyzing differential gene expression and signaling pathways, we aimed to understand the influence of ZNF296/Zfp296 on tumor-intrinsic mechanisms.
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Project description:Using a genome-wide CRISPR activation screen, we identified ZNF296, a transcription factor highly expressed in epithelial cancers, as a key regulator of tumor resistance to NK cell-mediated cytotoxicity. To uncover its direct targets, we performed ChIP-seq in A549 cells overexpressing ZNF296-Flag, revealing its preferential binding to specific genomic regions. IP-MS further demonstrated that ZNF296 interacts with the NuRD complex, which suppresses gene expression via histone deacetylase activity.To test whether ZNF296 mediates transcriptional repression through the NuRD complex, we conducted ChIP-seq for HDAC1, a core component of the complex, in ZNF296-overexpressing (ZNF296-OE) and control A549 cells. These analyses revealed genomic targets co-regulated by ZNF296 and the NuRD complex, providing insights into its mechanism of transcriptional regulation.
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