GSE168000
Oct4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human [RNA-seq}
Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their physical interactome in human ESCs (hESCs) has not been explored thus far. Here 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 core ATPases 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, in primed hESCs OCT4 cooperates with BRG1 and the transcription factor SOX2 to create an open chromatin architecture at neural lineage associted genes. This work offers insight into the regulation of human stem cell identity and reveals how a common transcription factor utilizes differential BAF complex composition to control distinct transcriptional programs in naive and primed hESCs. Overall design: To identify the functional roles of the core BAF ATPases, BRG1 and BRM, in human pluripotency, we performed RNA-seq analysis on BRG1-KO and BRM-KO naïve hESCs and BRG1-KO cells during the naive-to-primed transition.