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PPARγ phase separates with RXRα at PPREs to regulate target gene expression

Cell Discov. 2022-04; 
Zhean Li, Lingling Luo, Wenxia Yu, Ping Li, Danfeng Ou, Jia Liu, Hanhui Ma, Qinhu Sun, Aibin Liang, Cheng Huang, Tian Chi, Xingxu Huang, Yu Zhang
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摘要

Peroxisome proliferator-activated receptor (PPAR)-γ is a key transcription activator controlling adipogenesis and lipid metabolism. PPARγ binds PPAR response elements (PPREs) as the obligate heterodimer with retinoid X receptor (RXR) α, but exactly how PPARγ orchestrates the transcriptional response is unknown. This study demonstrates that PPARγ 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, PPARγ forms nuclear condensates at PPREs sites through phase separation to compartmentalize its heterodimer partner RXRα to initiate PPARγ-specific transcriptional activa... More

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