title: Role for human mediator subunit MED25 in recruitment of mediator to promoters by endoplasmic reticulum stress-responsive transcription factor ATF6α.
abstract: Transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. In response to ER stress, ATF6α translocates from its site of latency in the ER membrane to the nucleus, where it activates RNA polymerase II transcription of ER stress response genes upon binding sequence-specifically to ER stress response enhancer elements (ERSEs) in their promoter-regulatory regions. In a recent study, we demonstrated that ATF6α activates transcription of ER stress response genes by a mechanism involving recruitment to ERSEs of the multisubunit Mediator and several histone acetyltransferase (HAT) complexes, including Spt-Ada-Gcn5 (SAGA) and Ada-Two-A-containing (ATAC) (Sela, D., Chen, L., Martin-Brown, S., Washburn, M.P., Florens, L., Conaway, J.W., and Conaway, R.C. (2012) J. Biol. Chem. 287, 23035-23045). In this study, we extend our investigation of the mechanism by which ATF6α supports recruitment of Mediator to ER stress response genes. We present findings arguing that Mediator subunit MED25 plays a critical role in this process and identify a MED25 domain that serves as a docking site on Mediator for the ATF6α transcription activation domain.
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors.forename: Dotan
authors.initials: D
authors.lastname: Sela
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors.forename: Juliana J
authors.initials: JJ
authors.lastname: Conkright
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110,; Department of Biochemistry & Molecular Biology, Kansas University Medical Center, Kansas City, Kansas 66160, and.
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors.forename: Joshua
authors.initials: J
authors.lastname: Gilmore
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110,; Departments of Pathology & Laboratory Medicine, Kansas University Medical Center, Kansas City, Kansas 66160.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110,; Department of Biochemistry & Molecular Biology, Kansas University Medical Center, Kansas City, Kansas 66160, and.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
authors.affiliation: From the Stowers Institute for Medical Research, Kansas City, Missouri 64110,; Department of Biochemistry & Molecular Biology, Kansas University Medical Center, Kansas City, Kansas 66160, and. Electronic address: jlc@stowers.org.
authors.forename: Joan Weliky
authors.initials: JW
authors.lastname: Conaway
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D017434:Protein Structure, Tertiary
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C483045:MED25 protein, human; D056892:Mediator Complex; D009097:Multienzyme Complexes; D051548:Histone Acetyltransferases
keywords: Coactivator Transcription; Coregulator Transcription; Gene Regulation; RNA Polymerase II; Transcription Factors