Human TFIID binds to core promoter DNA in a reorganized structural state

Biophysics Graduate Group, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell (Impact Factor: 32.24). 01/2013; 152(1-2):120-131. DOI: 10.1016/j.cell.2012.12.005
Source: PubMed


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.

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Available from: Patricia Grob
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    • "Zhang et al. eLife 2015;4:e07777. DOI: 10.7554/eLife.07777 2 of 25 Research article Biochemistry | Genes and chromosomes Juven-Gershon et al., 2008; Liu et al., 2009; Cianfrocco et al., 2013 "
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    • "There is the added challenge that these complexes often adopt alternative configurations and conformations on promoter templates. However, recent improvements in high-resolution EM methods have led to some significant advances, including the structural determinations of the human TFIID complex and a nearly complete PIC (Cianfrocco et al., 2013; He et al., 2013; Liu et al., 2009; Murakami et al., 2013). EM structures of human TFIID bound to DNA revealed that this core component of the PIC induces even more dramatic turns of the promoter template than the binding of TBP to TATA DNA (Figure 3A). "
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    • "A major component lacking from the model in Figure 10 is the TFIID complex. Given the large size of TFIID and its welldocumented structural dynamics (Cianfrocco et al., 2013; Grob et al., 2006), several possibilities can be envisioned for how TFIID might assemble. Although the PIC model shown in Figure 10 is speculative and will likely be revised once additional data with larger PIC assemblies are obtained, it illustrates several important points. "
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