Human HP1BP3 regulates cortical neurogenesis and drives schizophrenia-like phenotypes

Here, we used integrative analyses of genome-wide association studies (GWAS) and single-cell transcriptomic datasets to identify HP1BP3, a heterochromatin-associated nuclear protein, as a schizophrenia-associated gene.

To investigate its functional role, we generated a Nestin-Cre–driven conditional knock-in mouse model expressing human HP1BP3 (hHP1BP3CKI mice). We performed CUT&Tag profiling of mouse brain tissue. And CUT&Tag profiling revealed that hHP1BP3 binding reshapes chromatin occupancy at transcription start sites and significantly downregulates the centrosomal protein CEP164, a key regulator of ciliogenesis and cell-cycle control.