TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation

Gabor Papai, Manish Tripathi, Christine Ruhlmann, Justin H. Layer, P. Anthony Weil, Patrick Schultz

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Transcription of eukaryotic messenger RNA (mRNA) encoding genes by RNA polymerase II (Pol II) is triggered by the binding of transactivating proteins to enhancer DNA, which stimulates the recruitment of general transcription factors (TFIIA, B, D, E, F, H) and Pol II on the cis-linked promoter, leading to pre-initiation complex formation and transcription. In TFIID-dependent activation pathways, this general transcription factor containing TATA-box-binding protein is first recruited on the promoter through interaction with activators and cooperates with TFIIA to form a committed pre-initiation complex. However, neither the mechanisms by which activation signals are communicated between these factors nor the structural organization of the activated pre-initiation complex are known. Here we used cryo-electron microscopy to determine the architecture of nucleoprotein complexes composed of TFIID, TFIIA, the transcriptional activator Rap1 and yeast enhancer-promoter DNA. These structures revealed the mode of binding of Rap1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by its interaction with Rap1. We propose that this change in position increases the exposure of TATA-box-binding protein within TFIID, consequently enhancing its ability to interact with the promoter. A large Rap1-dependent DNA loop forms between the activator-binding site and the proximal promoter region. This loop is topologically locked by a TFIIA-Rap1 protein bridge that folds over the DNA. These results highlight the role of TFIIA in transcriptional activation, define a molecular mechanism for enhancer-promoter communication and provide structural insights into the pathways of intramolecular communication that convey transcription activation signals through the TFIID complex.

Original languageEnglish (US)
Pages (from-to)956-960
Number of pages5
JournalNature
Volume465
Issue number7300
DOIs
StatePublished - Jun 17 2010

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Transcription Factor TFIIA
Transcription Factor TFIID
Trans-Activators
General Transcription Factors
TATA-Box Binding Protein
DNA
Transcriptional Activation
Cryoelectron Microscopy
Nucleoproteins
RNA Polymerase II
Genetic Promoter Regions
Carrier Proteins
Yeasts
Binding Sites
Messenger RNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Papai, G., Tripathi, M., Ruhlmann, C., Layer, J. H., Weil, P. A., & Schultz, P. (2010). TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation. Nature, 465(7300), 956-960. https://doi.org/10.1038/nature09080

TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation. / Papai, Gabor; Tripathi, Manish; Ruhlmann, Christine; Layer, Justin H.; Weil, P. Anthony; Schultz, Patrick.

In: Nature, Vol. 465, No. 7300, 17.06.2010, p. 956-960.

Research output: Contribution to journalArticle

Papai, G, Tripathi, M, Ruhlmann, C, Layer, JH, Weil, PA & Schultz, P 2010, 'TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation', Nature, vol. 465, no. 7300, pp. 956-960. https://doi.org/10.1038/nature09080
Papai, Gabor ; Tripathi, Manish ; Ruhlmann, Christine ; Layer, Justin H. ; Weil, P. Anthony ; Schultz, Patrick. / TFIIA and the transactivator Rap1 cooperate to commit TFIID for transcription initiation. In: Nature. 2010 ; Vol. 465, No. 7300. pp. 956-960.
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