OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human

Xin Huang, Kyoung mi Park, Paul Gontarz, Bo Zhang, Joshua Pan, Zachary McKenzie, Laura A. Fischer, Chen Dong, Sabine Dietmann, Xiaoyun Xing, Pavel V. Shliaha, Jihong Yang, Dan Li, Junjun Ding, Tenzin Lungjangwa, Maya Mitalipova, Shafqat A. Khan, Sumeth Imsoonthornruksa, Nick Jensen, Ting WangCigall Kadoch, Rudolf Jaenisch, Jianlong Wang, Thorold W. Theunissen

Research output: Contribution to journalArticlepeer-review

Abstract

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 interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes. In naïve hESCs, OCT4 is associated with both BRG1 and BRM, the two paralog ATPases of the BAF complex. Genome-wide location analyses and genetic studies reveal that these two enzymes cooperate in a functionally redundant manner in the transcriptional regulation of blastocyst-specific genes. In contrast, in primed hESCs, OCT4 cooperates with BRG1 and SOX2 to promote chromatin accessibility at ectodermal genes. This work reveals how a common transcription factor utilizes differential BAF complexes to control distinct transcriptional programs in naïve and primed hESCs.

Original languageEnglish
Article number5123
JournalNature communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021

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