CFP1

CFP1, short for CXXC finger protein 1, is a chromatin-associated protein that functions as a targeting subunit of the SET1/COMPASS histone H3K4 methyltransferase complexes. It binds DNA at unmethylated CpG dinucleotides through a CXXC-type zinc finger domain, enabling the preferential localization of the H3K4 methyltransferase to CpG island–rich promoter regions.

Biochemical role: As part of SET1A/SET1B complexes, CFP1 helps establish histone H3 lysine 4 methylation marks, typically associated with active transcription. By recognizing CpG islands, CFP1 directs the methyltransferase activity to promoter regions, contributing to the maintenance of gene expression programs during development and in differentiated cells. The protein itself does not methylate histones; it acts as a targeting and scaffolding component that coordinates with the WRAD core subunits.

Structure and interactions: CFP1 contains an N-terminal CXXC domain that binds unmethylated CpG DNA. It associates with core components of the WRAD subcomplex, including WDR5, RBBP5, ASH2L, and DPY30, to form the catalytic SET1/COMPASS assemblies. It can also interact with other regulatory factors that influence promoter activity and chromatin state.

Biological significance: CFP1 is evolutionarily conserved and plays a critical role in development. In model systems, loss of CFP1 disrupts global H3K4me3 deposition at promoters and can lead to developmental defects. Dysregulation of CpG island methylation and H3K4 methylation patterns is linked to various diseases, including cancer, where CFP1-related pathways may be altered.