title: Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.
abstract: The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA.
authors.forename: Dotan
authors.initials: D
authors.lastname: Sela
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Skylar
authors.initials: S
authors.lastname: Martin-Brown
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Joan Weliky
authors.initials: JW
authors.lastname: Conaway
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Conaway
mesh_terms: D051702:Activating Transcription Factor 6 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002843:Chromatin / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D056892:Mediator Complex / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D002843:Chromatin; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D056892:Mediator Complex; D051548:Histone Acetyltransferases; D012319:RNA Polymerase II