机构：[1]School of Life Science and Technology, ShanghaiTech University, Shanghai, China.[2]Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.[3]School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.[4]Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China.[5]International Academy of Optoelectronics at Zhaoqing, South China Normal University, Zhaoqing, Guangdong, China.[6]Shanghai R&D Center for Standardization of Chinese Medicines, Shanghai, China.[7]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China浙江大学医学院附属第一医院
Peroxisome proliferator-activated receptor (PPAR)-gamma is a key transcription activator controlling adipogenesis and lipid metabolism. PPAR gamma binds PPAR response elements (PPREs) as the obligate heterodimer with retinoid X receptor (RXR) alpha, but exactly how PPAR gamma orchestrates the transcriptional response is unknown. This study demonstrates that PPAR gamma forms phase-separated droplets in vitro and solid-like nuclear condensates in cell, which is intriguingly mediated by its DNA binding domain characterized by the zinc finger motif. Furthermore, PPAR gamma forms nuclear condensates at PPREs sites through phase separation to compartmentalize its heterodimer partner RXR alpha to initiate PPAR gamma-specific transcriptional activation. Finally, using an optogenetic approach, the enforced formation of PPAR gamma/RXR alpha condensates leads to preferential enrichment at PPREs sites and significantly promotes the expression of PPAR gamma target genes. These results define a novel mechanism by which PPAR gamma engages the phase separation principles for efficient and specific transcriptional activation.
基金：
National Key R&D Program of China [2021YFA0804702]; National Natural Science Foundation of China [81830004]; leading talents of Guangdong province program [608285568031]
第一作者机构：[1]School of Life Science and Technology, ShanghaiTech University, Shanghai, China.[2]Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
共同第一作者：
通讯作者：
通讯机构：[1]School of Life Science and Technology, ShanghaiTech University, Shanghai, China.[7]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
推荐引用方式(GB/T 7714)：
Li Zhean,Luo Lingling,Yu Wenxia,et al.PPAR gamma phase separates with RXR alpha at PPREs to regulate target gene expression[J].CELL DISCOVERY.2022,8(1):doi:10.1038/s41421-022-00388-0.
APA：
Li, Zhean,Luo, Lingling,Yu, Wenxia,Li, Ping,Ou, Danfeng...&Zhang, Yu.(2022).PPAR gamma phase separates with RXR alpha at PPREs to regulate target gene expression.CELL DISCOVERY,8,(1)
MLA：
Li, Zhean,et al."PPAR gamma phase separates with RXR alpha at PPREs to regulate target gene expression".CELL DISCOVERY 8..1(2022)
生物学