Two target gene activation pathways for orphan ERR nuclear receptors

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buir.contributor.authorCevher, Murat Alper
buir.contributor.orcidCevher, Murat Alper|0000-0002-2663-1172
dc.citation.epage183en_US
dc.citation.issueNumber2
dc.citation.spage165
dc.citation.volumeNumber33
dc.contributor.authorNakadai, T.
dc.contributor.authorShimada, M.
dc.contributor.authorIto, K.
dc.contributor.authorCevher, Murat Alper
dc.contributor.authorChu, C.-S.
dc.contributor.authorKumegawa, K.
dc.contributor.authorMaruyama, R.
dc.contributor.authorMalik, S.
dc.contributor.authorRoeder, R. G.
dc.date.accessioned2024-03-18T11:12:53Z
dc.date.available2024-03-18T11:12:53Z
dc.date.issued2023-01-16
dc.departmentDepartment of Molecular Biology and Genetics
dc.description.abstractEstrogen-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-1α may also be fulfilled by other AF2-interacting coactivators like NCOA3, which is shown to recruit Mediator selectively to ERRβ and 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.
dc.identifier.doi10.1038/s41422-022-00774-z
dc.identifier.eissn1748-7838
dc.identifier.issn1001-0602
dc.identifier.urihttps://hdl.handle.net/11693/114884
dc.language.isoEnglish
dc.publisherNature Publishing Group
dc.relation.isversionofhttps://dx.doi.org/10.1038/s41422-022-00774-z
dc.source.titleCell Research
dc.titleTwo target gene activation pathways for orphan ERR nuclear receptors
dc.typeArticle

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