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Regulatory interplay between TFIID's conformational transitions and its modular interaction with core promoter DNA.

Cianfrocco MA, Nogales E - Transcription (2013)

Bottom Line: Recent structural and biochemical studies of human TFIID have significantly increased our understanding of the mechanisms underlying the recruitment of TFIID to promoter DNA and its role in transcription initiation.Here we propose a general model of promoter binding by TFIID, where co-activators, activators, and histone modifications promote and/or stabilize a conformational state of TFIID that results in core promoter engagement.Within this high affinity conformation, we propose that TFIID's extensive interaction with promoter DNA leads to topological changes in the DNA that facilitate the eventual loading of RNAP II.

View Article: PubMed Central - PubMed

Affiliation: Biophysics Graduate Group; University of California; Berkeley, CA USA.

ABSTRACT
Recent structural and biochemical studies of human TFIID have significantly increased our understanding of the mechanisms underlying the recruitment of TFIID to promoter DNA and its role in transcription initiation. Structural studies using cryo-EM revealed that modular interactions underlie TFIID's ability to bind simultaneously multiple promoter motifs and to define a DNA state that will facilitate transcription initiation. Here we propose a general model of promoter binding by TFIID, where co-activators, activators, and histone modifications promote and/or stabilize a conformational state of TFIID that results in core promoter engagement. Within this high affinity conformation, we propose that TFIID's extensive interaction with promoter DNA leads to topological changes in the DNA that facilitate the eventual loading of RNAP II. While more work is required to dissect the individual contributions of activators and repressors to TFIID's DNA binding, the recent cryo-EM studies provide a physical framework to guide future structural, biophysical, and biochemical experiments.

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Figure 2. Regulatory interplay between co-activators, activators, histone modifications and promoter DNA binding by TFIID. (A) TFIID exists in both canonical and rearranged conformational states, but only the rearranged state interacts efficiently with SCP DNA. Without TFIIA, TFIID interacts only with SCP and SCP(mTATA) (left). TFIIA facilitates TFIID binding to all mutant promoters (right). (B) TATA box DNA, p53, and H3K4me3 likely stabilize TFIID in a rearranged conformation, as these factors cooperatively stimulate transcription initiation by TFIID. Adapted from.43
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Figure 2: Figure 2. Regulatory interplay between co-activators, activators, histone modifications and promoter DNA binding by TFIID. (A) TFIID exists in both canonical and rearranged conformational states, but only the rearranged state interacts efficiently with SCP DNA. Without TFIIA, TFIID interacts only with SCP and SCP(mTATA) (left). TFIIA facilitates TFIID binding to all mutant promoters (right). (B) TATA box DNA, p53, and H3K4me3 likely stabilize TFIID in a rearranged conformation, as these factors cooperatively stimulate transcription initiation by TFIID. Adapted from.43

Mentions: The cryo-EM structure of TFIID-TFIIA-DNA indicates that TFIID utilizes two distinct sites of interaction with promoter DNA. A bipartite model of promoter recognition by TFIID is supported by in vivo and in vitro analysis of TFIID complex integrity. Through a systematic depletion of each subunit of TFIID using RNA interference, a stable core subcomplex of TFIID was identified that comprises subunits TAF4, -5, -6, -9, -12, as knockdown of any of these subunits resulted in the concomitant loss of protein expression for the entire TFIID complex.28 We believe that this core complex corresponds to our structurally defined BC core (Fig. 1A, dotted line), which is capable of interacting with MTE/DPE motifs. As accessory subunits to the core TFIID subcomplex, subunits TAF1, TAF2, TBP, and TAF11 were characterized as components that were dispensable for formation of the core subcomplex. Therefore, as indicated above, we propose this subcomplex to correspond to the flexibly attached lobe A. These lobe assignments are supportive of a model of promoter binding whereby TFIID interacts with upstream and downstream promoter motifs via two distinct structural modules: binding of MTE/DPE by TAF6 and TAF9 within the stable BC core, and upstream DNA binding by the TBP-containing lobe A (Fig. 2A).


Regulatory interplay between TFIID's conformational transitions and its modular interaction with core promoter DNA.

Cianfrocco MA, Nogales E - Transcription (2013)

Figure 2. Regulatory interplay between co-activators, activators, histone modifications and promoter DNA binding by TFIID. (A) TFIID exists in both canonical and rearranged conformational states, but only the rearranged state interacts efficiently with SCP DNA. Without TFIIA, TFIID interacts only with SCP and SCP(mTATA) (left). TFIIA facilitates TFIID binding to all mutant promoters (right). (B) TATA box DNA, p53, and H3K4me3 likely stabilize TFIID in a rearranged conformation, as these factors cooperatively stimulate transcription initiation by TFIID. Adapted from.43
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4042585&req=5

Figure 2: Figure 2. Regulatory interplay between co-activators, activators, histone modifications and promoter DNA binding by TFIID. (A) TFIID exists in both canonical and rearranged conformational states, but only the rearranged state interacts efficiently with SCP DNA. Without TFIIA, TFIID interacts only with SCP and SCP(mTATA) (left). TFIIA facilitates TFIID binding to all mutant promoters (right). (B) TATA box DNA, p53, and H3K4me3 likely stabilize TFIID in a rearranged conformation, as these factors cooperatively stimulate transcription initiation by TFIID. Adapted from.43
Mentions: The cryo-EM structure of TFIID-TFIIA-DNA indicates that TFIID utilizes two distinct sites of interaction with promoter DNA. A bipartite model of promoter recognition by TFIID is supported by in vivo and in vitro analysis of TFIID complex integrity. Through a systematic depletion of each subunit of TFIID using RNA interference, a stable core subcomplex of TFIID was identified that comprises subunits TAF4, -5, -6, -9, -12, as knockdown of any of these subunits resulted in the concomitant loss of protein expression for the entire TFIID complex.28 We believe that this core complex corresponds to our structurally defined BC core (Fig. 1A, dotted line), which is capable of interacting with MTE/DPE motifs. As accessory subunits to the core TFIID subcomplex, subunits TAF1, TAF2, TBP, and TAF11 were characterized as components that were dispensable for formation of the core subcomplex. Therefore, as indicated above, we propose this subcomplex to correspond to the flexibly attached lobe A. These lobe assignments are supportive of a model of promoter binding whereby TFIID interacts with upstream and downstream promoter motifs via two distinct structural modules: binding of MTE/DPE by TAF6 and TAF9 within the stable BC core, and upstream DNA binding by the TBP-containing lobe A (Fig. 2A).

Bottom Line: Recent structural and biochemical studies of human TFIID have significantly increased our understanding of the mechanisms underlying the recruitment of TFIID to promoter DNA and its role in transcription initiation.Here we propose a general model of promoter binding by TFIID, where co-activators, activators, and histone modifications promote and/or stabilize a conformational state of TFIID that results in core promoter engagement.Within this high affinity conformation, we propose that TFIID's extensive interaction with promoter DNA leads to topological changes in the DNA that facilitate the eventual loading of RNAP II.

View Article: PubMed Central - PubMed

Affiliation: Biophysics Graduate Group; University of California; Berkeley, CA USA.

ABSTRACT
Recent structural and biochemical studies of human TFIID have significantly increased our understanding of the mechanisms underlying the recruitment of TFIID to promoter DNA and its role in transcription initiation. Structural studies using cryo-EM revealed that modular interactions underlie TFIID's ability to bind simultaneously multiple promoter motifs and to define a DNA state that will facilitate transcription initiation. Here we propose a general model of promoter binding by TFIID, where co-activators, activators, and histone modifications promote and/or stabilize a conformational state of TFIID that results in core promoter engagement. Within this high affinity conformation, we propose that TFIID's extensive interaction with promoter DNA leads to topological changes in the DNA that facilitate the eventual loading of RNAP II. While more work is required to dissect the individual contributions of activators and repressors to TFIID's DNA binding, the recent cryo-EM studies provide a physical framework to guide future structural, biophysical, and biochemical experiments.

Show MeSH