CFP1 regulating genomic H3K4me3 signature reshaping links to lung adenocarcinoma progression

Histone H3 lysine 4 trimethylation (H3K4me3) is a canonical chromatin modification linked to active gene transcription and responsible for the extensive regulation of cell functions. Several components of the H3K4me3 methyltransferase complex of proteins associated with SET1 (COMPASS) have been proposed to mediate cancer-protective or cancer-inhibitive effects through specific inducive H3K4me3 modification. However, the role of the indispensable non-catalytic component of COMPASS CXXC-type zinc finger protein 1 (CFP1) in malignant advance is unclear. CFP1 deficiency led to dual effects on cancer cell transcriptome including extensive inactivation of cancer-promoting as well as activation of cancer repressors. Combined with the chromatin immunoprecipitation sequencing (ChIP-seq) analysis, we showed that CFP1 ablation reshaped the genomic H3K4me3 distribution signature, and TGF-b and WNT signaling pathways were dominant targets.