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 Wang, Cigall Kadoch, Rudolf Jaenisch, Jianlong Wang () and Thorold W. Theunissen ()
Additional contact information
Xin Huang: Columbia University Irving Medical Center
Kyoung-mi Park: Washington University School of Medicine
Paul Gontarz: Washington University School of Medicine
Bo Zhang: Washington University School of Medicine
Joshua Pan: Dana-Farber Cancer Institute
Zachary McKenzie: Dana-Farber Cancer Institute
Laura A. Fischer: Washington University School of Medicine
Chen Dong: Washington University School of Medicine
Sabine Dietmann: Washington University School of Medicine
Xiaoyun Xing: Washington University School of Medicine
Pavel V. Shliaha: Memorial Sloan Kettering Cancer Center
Jihong Yang: Columbia University Irving Medical Center
Dan Li: Columbia University Irving Medical Center
Junjun Ding: Icahn School of Medicine at Mount Sinai
Tenzin Lungjangwa: Whitehead Institute for Biomedical Research
Maya Mitalipova: Whitehead Institute for Biomedical Research
Shafqat A. Khan: Washington University School of Medicine
Sumeth Imsoonthornruksa: Whitehead Institute for Biomedical Research
Nick Jensen: Washington University School of Medicine
Ting Wang: Washington University School of Medicine
Cigall Kadoch: Dana-Farber Cancer Institute
Rudolf Jaenisch: Whitehead Institute for Biomedical Research
Jianlong Wang: Columbia University Irving Medical Center
Thorold W. Theunissen: Washington University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25107-3

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