OCT4 cooperates with distinct chromatin remodelers in naive and primed pluripotent states in human [ChIP-Seq]

Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). We mapped the protein-protein interactions of OCT4 in naive and primed hESCs, revealing extensive connections to ATP-dependent nucleosome remodeling complexes. In naive hESCs, OCT4 is associated with both BRG1 and BRM, the two mutually exclusive ATPase subunits of the BAF complex. Genome-wide location analyses and genetic deletion studies reveal that these two enzymes exert a functionally redundant role in transcriptional regulation of blastocyst-specific genes. In contrast, OCT4 cooperates with BRG1 and the transcription factor SOX2 to create an open chromatin architecture at neural lineage-associated genes in primed hESCs. This work offers insight into the regulation of human stem cell identity and reveals how a common transcription factor utilizes differential compositions of the BAF complex in controlling distinct transcriptional programs governing naive vs. primed human pluripotent states. Overall design: Genome binding/occupancy profiling of chromatin remodelers BAF155, BRG1, BRM, and transcription factors SOX2 in naive and primed hESCs by ChIP sequencing. Transcriptomes of naive and primed hESCs upon knockdown of either BRG1 or BRM by RNA sequencing.