Hao-Fountain syndrome protein USP7 controls neuronal differentiation via BCOR-ncPRC1.1.

ABSTRACT: Pathogenic variants in the ubiquitin-specific protease 7 (USP7) gene cause a neurodevelopmental disorder called Hao-Fountain syndrome. However, it remains unclear which of USP7's pleiotropic functions are relevant for neurodevelopment. Here, we present a combination of quantitative proteomics, transcriptomics, and epigenomics to define the USP7 regulatory circuitry during neuronal differentiation. USP7 activity is required for the transcriptional programs that direct both the differentiation of embryonic stem cells into neural stem cells and the neuronal differentiation of SH-SY5Y neuroblastoma cells. USP7 controls the dosage of the Polycomb monubiquitylated histone H2A lysine 119 (H2AK119ub1) ubiquitin ligase complexes ncPRC1.1 and ncPRC1.6. Loss-of-function experiments revealed th

SUBMITTER: Wolf van der Meer J 

PROVIDER: S-EPMC11875088 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature