POGZ controls embryonic stem cell self-renewal and pluripotency by association with esBAF and HP1
POGZ, which encodes a multi-domain transcription factor, has been found frequently mutated in neurodevelopmental disorders, particularly autism spectrum disorder (ASD) and intellectual disability (ID). However, little is known about its functions in embryonic stem cells (ESCs) and in transcriptional regulation. Here, we show that POGZ plays key roles in the maintenance of ESCs by association with the SWI-SNF (BAF) chromatin remodeler complex and heterochromatin protein 1 (HP1) proteins. Loss of POGZ induces differentiation of ESCs, likely by up-regulation of primitive endoderm and mesoderm lineage genes and by down-regulation of pluripotency-related and cell cycle genes. Genome-wide binding analysis shows that POGZ is primarily localized to gene promoter and enhancer regions where POGZ is required to maintain an open chromatin. Regulation of chromatin under control of POGZ depends on esBAF complex. Furthermore, there is an extensive overlap of POGZ and OCT4 peaks genome-wide, and both factors interact with each other. We propose that POGZ is an important pluripotency-associated factor, and its absence causes failure to maintain a proper ESC-specific chromatin state and transcriptional circuitry, which eventually leads to loss of ESC phenotype. Our work provides important insights into the roles of POGZ in the maintenance of ESC identity as well as regulation of transcription, which will be useful for understanding the etiology of neurodevelopmental disorders by POGZ mutation.