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

doi:10.1038/s41421-022-00388-0

	PPARγ phase separates with RXRα at PPREs to regulate target gene expression
	Li, Zhean1,2 ; Luo, Lingling 3; Yu, Wenxia1 ; Li, Ping 4; Ou, Danfeng 5; Liu, Jia2 ; Ma, Hanhui1 ; Sun, Qinhu 6; Liang, Aibin 4; Huang, Cheng 3; Chi, Tian1 ; Huang, Xingxu1,7 ; Zhang, Yu1
	2022-04-26
发表期刊	CELL DISCOVERY
ISSN	2056-5968
EISSN	2056-5968
卷号	8 期号:1
发表状态	已发表
DOI	10.1038/s41421-022-00388-0
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 activation. Finally, using an optogenetic approach, the enforced formation of PPARγ/RXRα condensates leads to preferential enrichment at PPREs sites and significantly promotes the expression of PPARγ target genes. These results define a novel mechanism by which PPARγ engages the phase separation principles for efficient and specific transcriptional activation.
URL	查看原文
收录类别	SCIE
语种	英语
Scopus 记录号	2-s2.0-85128913461
来源库	Scopus
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/185372
专题	免疫化学研究所_PI研究组_刘佳组生命科学与技术学院_PI研究组_池天组生命科学与技术学院_PI研究组_黄行许组生命科学与技术学院_博士生生命科学与技术学院_PI研究组_马涵慧组
通讯作者	Huang, Xingxu; Zhang, Yu
作者单位	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
第一作者单位	生命科学与技术学院; 免疫化学研究所
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Zhean,Luo, Lingling,Yu, Wenxia,et al. PPARγ phase separates with RXRα at PPREs to regulate target gene expression[J]. CELL DISCOVERY,2022,8(1).
APA	Li, Zhean.,Luo, Lingling.,Yu, Wenxia.,Li, Ping.,Ou, Danfeng.,...&Zhang, Yu.(2022).PPARγ phase separates with RXRα at PPREs to regulate target gene expression.CELL DISCOVERY,8(1).
MLA	Li, Zhean,et al."PPARγ phase separates with RXRα at PPREs to regulate target gene expression".CELL DISCOVERY 8.1(2022).