ZEB2 functions in great ape B lymphoblastoid cells

Despite nearly identical protein-coding sequences, humans exhibit distinct phenotypic differences from other primates. Understanding these species-specific traits and adaptations requires investigating changes in transcriptional regulation. In this study, we focus on ZEB2, a ubiquitously expressed transcription factor (TF) with critical roles in the immune system and neural development, and compare its regulatory activity across great apes. Using B-lymphoblastoid cells from humans, chimpanzees, and orangutans, we generated genome-wide ChIP-Seq data to map ZEB2 binding sites. Our analysis revealed consistent ZEB2 binding near transcription start sites, with conserved and human-specific binding events. Functional knockdown of ZEB2 in these cells followed by gene expression profiling uncovered human-specific regulatory differences, particularly in genes associated with nervous system development.