TY - JOUR
T1 - OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human
AU - Huang, Xin
AU - Park, Kyoung mi
AU - Gontarz, Paul
AU - Zhang, Bo
AU - Pan, Joshua
AU - McKenzie, Zachary
AU - Fischer, Laura A.
AU - Dong, Chen
AU - Dietmann, Sabine
AU - Xing, Xiaoyun
AU - Shliaha, Pavel V.
AU - Yang, Jihong
AU - Li, Dan
AU - Ding, Junjun
AU - Lungjangwa, Tenzin
AU - Mitalipova, Maya
AU - Khan, Shafqat A.
AU - Imsoonthornruksa, Sumeth
AU - Jensen, Nick
AU - Wang, Ting
AU - Kadoch, Cigall
AU - Jaenisch, Rudolf
AU - Wang, Jianlong
AU - Theunissen, Thorold W.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) Director’s New Innovator Award (DP2 GM137418) and a grant from the Children’s Discovery Institute (CDI-LI-2019-819) to T.W.T. and grants from the NIH (1R01GM129157, 1R01HD095938, and 1R01HD097268) and New York State (NYSTEM) (C32583GG and C32569GG) to J.W. S.I. was funded by the Suranaree University of Technology under the National Research University (NRU) project of Thailand, Office of the Higher Education Commission. We thank Frank Soldner and Haoyi Wang for advice on gene targeting, Qing Gao for assistance with teratoma analysis, Angela Bowman and Lilianna Solnica-Krezel for critical reading of the manuscript, the Genome Engineering and iPSC Center (GEiC) at the Washington University School of Medicine (WUSM) for gRNA validation services, and the Genome Technology Access Center (GTAC) in the Department of Genetics at WUSM for help with genome sequencing. GTAC is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1 TR000448 from the National Center for Research Resources (NCRR), a component of the NIH, and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. All experiments involving hESCs were approved by the Institutional Biological and Chemical Safety Committee and Embryonic Stem Cell Research Oversight Committee at Washington University School of Medicine and Columbia University Irving Medical Center.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113423676&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-25107-3
DO - 10.1038/s41467-021-25107-3
M3 - Article
C2 - 34446700
AN - SCOPUS:85113423676
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5123
ER -