Two target gene activation pathways for orphan ERR nuclear receptors  

作　　者：Tomoyoshi Nakadai Miho Shimada Keiichi Ito Murat Alper Cevher Chi-Shuen Chu Kohei Kumegawa Reo Maruyama Sohail Malik Robert G Roeder 

机构地区：[1]Laboratory of Biochemistry and Molecular Biology,The Rockefeller University,New York,NY,USA [2]Project for Cancer Epigenomics,Cancer Institute,Japanese Foundation for Cancer Research,Tokyo,Japan [3]Department of Molecular Biology,Yokohama City University Graduate School of Medical Science,Yokohama,Japan [4]Department of Molecular Biology and Genetics,Bilkent University,Ankara,Turkey [5]Cancer Cell Diversity Project,NEXT-Ganken Program,Japanese Foundation for Cancer Research,Tokyo,Japan

出　　处：《Cell Research》2023年第2期165-183,共19页细胞研究（英文版）

基　　金：NIH grants DK071900 and CACA234575 to R.G.R.T.N.was supported by JSPS KAKENHI(19K07651);M.S.was supported by JSPS KAKENHI(19K06482);K.I.by an NCI T32 grant(CA009673);JSPS fellowship for research abroad;M.A.C.by an American Cancer Society Eastern Division-New York Cancer Research Fund Postdoctoral Fellowship.

摘　　要：Estrogen-related receptors(ERRα/β/γ)are orphan nuclear receptors that function in energy-demanding physiological processes,as well as in development and stem cell maintenance,but mechanisms underlying target gene activation by ERRs are largely unknown.Here,reconstituted biochemical assays that manifest ERR-dependent transcription have revealed two complementary mechanisms.On DNA templates,ERRs activate transcription with just the normal complement of general initiation factors through an interaction of the ERR DNA-binding domain with the p52 subunit of initiation factor TFIIH.On chromatin templates,activation by ERRs is dependent on AF2 domain interactions with the cell-specific coactivator PGC-1α,which in turn recruits the ubiquitous p300 and MED1/Mediator coactivators.This role of PGC-1αmay also be fulfilled by other AF2-interacting coactivators like NCOA3,which is shown to recruit Mediator selectively to ERRβand ERRγ.Importantly,combined genetic and RNA-seq analyses establish that both the TFIIH and the AF2 interaction-dependent pathways are essential for ERRβ/γ-selective gene expression and pluripotency maintenance in embryonic stem cells in which NCOA3 is a critical coactivator.

关 键 词：ACTIVATION TEMPLATE ERR 

分 类 号：R33[医药卫生—人体生理学]