ZNF304 is a KRAB-containing zinc finger transcription factor that functions as a chr19-based repressor with roles in cancer and viral latency. Primary Function: ZNF304 acts as a transcriptional repressor, recruiting corepressor complexes to target gene promoters 1. In colorectal cancer cells with activated KRAS, ZNF304 mediates promoter hypermethylation and silencing of tumor suppressors including p14(ARF), p15(INK4B), and p16(INK4A) by recruiting DNMT1 and SETDB1 1. In embryonic stem cells, ZNF304 maintains transcriptional repression through H3K27me3 trimethylation via polycomb group complex recruitment 1. Mechanism: ZNF304 binds at promoter regions and associates with TRIM28, forming repressive chr19 complexes containing methyltransferases and polycomb repression factors 12. In ovarian cancer, ZNF304 positively regulates β1 integrin transcription, promoting cell migration, proliferation, and anoikis resistance through integrin-mediated signaling 3. Disease Relevance: ZNF304 expression correlates with poor overall survival in ovarian cancer and enables tumor growth 3. In HIV-infected cells, ZNF304 silences viral transcription and promotes latency by recruiting repressive complexes to the HIV promoter 2. Clinical Significance: ZNF304 hypermethylation serves as a CRC-specific biomarker with 85.7-94.3% diagnostic accuracy and potential utility in cell-free DNA screening 45.