The NuRD complex cooperates with SALL4 to orchestrate reprogramming

Bo Wang, Chen Li, Jin Ming, Linlin Wu, Shicai Fang, Yi Huang, Lihui Lin, He Liu, Junqi Kuang, Chengchen Zhao, Xingnan Huang, Huijian Feng, Jing Guo, Xuejie Yang, Liman Guo, Xiaofei Zhang, Jiekai Chen, Jing Liu, Ping Zhu () and Duanqing Pei ()
Additional contact information
Bo Wang: Westlake University
Chen Li: South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Jin Ming: Westlake University
Linlin Wu: Westlake University
Shicai Fang: South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Yi Huang: South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Lihui Lin: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
He Liu: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Junqi Kuang: Westlake University
Chengchen Zhao: Westlake University
Xingnan Huang: Westlake University
Huijian Feng: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Jing Guo: South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Xuejie Yang: South China Institutes for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
Liman Guo: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Xiaofei Zhang: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Jiekai Chen: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Jing Liu: Guangzhou Regenerative Medicine and Health Guangdong Laboratory
Ping Zhu: Southern Medical University
Duanqing Pei: Westlake University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Cell fate decision involves rewiring of the genome, but remains poorly understood at the chromatin level. Here, we report that chromatin remodeling complex NuRD participates in closing open chromatin in the early phase of somatic reprogramming. Sall4, Jdp2, Glis1 and Esrrb can reprogram MEFs to iPSCs efficiently, but only Sall4 is indispensable capable of recruiting endogenous components of NuRD. Yet knocking down NuRD components only reduces reprogramming modestly, in contrast to disrupting the known Sall4-NuRD interaction by mutating or deleting the NuRD interacting motif at its N-terminus that renders Sall4 inept to reprogram. Remarkably, these defects can be partially rescured by grafting NuRD interacting motif onto Jdp2. Further analysis of chromatin accessibility dynamics demonstrates that the Sall4-NuRD axis plays a critical role in closing the open chromatin in the early phase of reprogramming. Among the chromatin loci closed by Sall4-NuRD encode genes resistant to reprogramming. These results identify a previously unrecognized role of NuRD in reprogramming, and may further illuminate chromatin closing as a critical step in cell fate control.

Date: 2023
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DOI: 10.1038/s41467-023-38543-0

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