ZFPs

Zinc finger proteins (ZFPs) are a large and diverse family of proteins defined by the presence of zinc finger motifs, which coordinate zinc ions to stabilize folds that can bind DNA, RNA, or other proteins. The most common DNA-binding domains are C2H2-type zinc fingers, arranged in tandem arrays to recognize longer DNA sequences. Some ZFPs also contain additional domains, such as KRAB, SCAN, or BTB/POZ, that influence function and interactions.

Many ZFPs act as transcription factors that regulate gene expression by binding specific regulatory DNA elements, including promoters and enhancers. Depending on the context and partner proteins, ZFPs can activate or repress transcription. A prominent subgroup, the KRAB-ZFPs, recruits the corepressor KAP1 (TRIM28) and a histone methyltransferase to establish repressive chromatin and silence target genes, including transposable elements. Other ZFPs function as cofactors or scaffolds within chromatin-modifying complexes.

ZFPs form one of the largest vertebrate gene families, with hundreds of genes in humans. They have undergone rapid birth-and-death evolution and lineage-specific diversification, a pattern linked to the control of regulatory networks and genomic parasites such as transposable elements.

ZFPs participate in development, differentiation, stem cell biology, metabolism, and stress responses. Aberrant ZFP activity or mutations have been connected to developmental disorders and cancer, among other conditions.

Zinc finger domains have been engineered for targeted genome manipulation, notably in zinc finger nucleases (ZFNs), one of the early genome-editing tools, though other technologies have since become more prevalent.