ZNF787 recognizes the core sequence of MIR element to regulate gene expression

Zinc finger (ZNF) proteins are widely studied as DNA-binding transcriptional regulators, yet many remain functionally uncharacterized, particularly in the context of repetitive genomic regions. Here, we report that ZNF787 specifically binds a conserved 9-bp core motif within mammalian-wide interspersed repeats (MIRs) and interacts with the nucleosome remodeling and deacetylase (NuRD) complex. Depletion of ZNF787 leads to de-repression of nearby genes accompanied by increased local H3K27ac levels. Genetic rescue experiments confirm that the C2H2 zinc-finger domain of ZNF787 is essential for this repression. Thus, our research identifies ZNF787 as a repressor that binds MIR elements and interacts with the NuRD complex to mediate repeat-directed transcriptional silencing. This finding expands the functional repertoire of ZNF proteins and illustrates how specific repetitive sequences can encode local epigenetic regulatory information.