Objective TRIM28 (TRIpartate motif-containing protein 28), also called KAP1 (KRAB-associated protein1) or TIF1β (transcription intermediary factor 1β), is a heterochromatin related protein, composed of RBCC domain in N terminal and PHD,BROMO,NHD domain in C terminal, which participates in the establishment of H3K9me3 modification and SUMOylation pathway. The present study is to further explore the function of TRIM28.Methods We used CRISPR/cas9 technology, chromatin imm unoprecipitation assay, Western blot, quantitative real-time assay in HEK293F cell line to further study the function of TRIM28. We knocked out Trim28 gene in HEK293F cell line by CRISPR/cas9 technology.Results By analyzing experimental data, we found that TRIM28 mainly suppresses the transcription of genes with low endogenous expression level. Further analysis by GO bioinformation assay, we found that TRIM28 regulates zinc finger protein family genes and protocadherin protein family genes. According to the results of ChIP-seq, we found that in Trim28 knockout cell lines, the global distribution pattern of H3K9me3 decreased dramatically and H3K4me3 dropped moderately in TRIM28 target sites, indicating TRIM28 not only regulates the establishment of heterochromatin but also affects cis-acting elements. Meanwhile, H3K27ac modification, H3K4me1 modification and H3K4me3 modification in zinc finger protein family genes increased significantly, H3K9me3 decreased dramatically. H3K4me3 modification in protocadherin protein family genes increased significantly, H3K9me3 decreased dramatically. Previous study showed that protocadherin protein family genes mainly engaged in the identification and recognition of axon and dendrites in neuron cell.Conclusion In our study, it’s the first time to show the relationship between TRIM28 and protocadherin protein family genes. These results suggest that TRIM28 regulates zinc finger and protocadherin β genes by changing the chromatin accessibility and provide a new idea for further study of the relationship between TRIM28 and chromatin higher order structure.