title: Human TFIID binds to core promoter DNA in a reorganized structural state.
abstract: A mechanistic description of metazoan transcription is essential for understanding the molecular processes that govern cellular decisions. To provide structural insights into the DNA recognition step of transcription initiation, we used single-particle electron microscopy (EM) to visualize human TFIID with promoter DNA. This analysis revealed that TFIID coexists in two predominant and distinct structural states that differ by a 100 Å translocation of TFIID's lobe A. The transition between these structural states is modulated by TFIIA, as the presence of TFIIA and promoter DNA facilitates the formation of a rearranged state of TFIID that enables promoter recognition and binding. DNA labeling and footprinting, together with cryo-EM studies, were used to map the locations of TATA, Initiator (Inr), motif ten element (MTE), and downstream core promoter element (DPE) promoter motifs within the TFIID-TFIIA-DNA structure. The existence of two structurally and functionally distinct forms of TFIID suggests that the different conformers may serve as specific targets for the action of regulatory factors.
authors: Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Michael A
authors: MA
authors: Cianfrocco
authors: George A
authors: GA
authors: Kassavetis
authors: Patricia
authors: P
authors: Grob
authors: Jie
authors: J
authors: Fang
authors: Tamar
authors: T
authors: Juven-Gershon
authors: James T
authors: JT
authors: Kadonaga
authors: Eva
authors: E
authors: Nogales
mesh_terms: D020285:Cryoelectron Microscopy; D004247:DNA / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D016385:TATA Box; D035561:Transcription Factor TFIIA / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D035561:Transcription Factor TFIIA; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D004247:DNA; D012319:RNA Polymerase II