Publikationsdatum:
2010-06-19
Beschreibung:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900199/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900199/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Papai, Gabor -- Tripathi, Manish K -- Ruhlmann, Christine -- Layer, Justin H -- Weil, P Anthony -- Schultz, Patrick -- GM52461/GM/NIGMS NIH HHS/ -- R01 GM052461/GM/NIGMS NIH HHS/ -- R01 GM052461-14/GM/NIGMS NIH HHS/ -- England -- Nature. 2010 Jun 17;465(7300):956-60. doi: 10.1038/nature09080.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Structural Biology and Genomics, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP10142, 67404 Illkirch, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20559389" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Cryoelectron Microscopy
;
*Models, Molecular
;
Nucleoproteins/chemistry/ultrastructure
;
Protein Structure, Tertiary
;
Saccharomyces cerevisiae
;
Saccharomyces cerevisiae Proteins/chemistry/*metabolism/ultrastructure
;
Telomere-Binding Proteins/chemistry/*metabolism/ultrastructure
;
Transcription Factor TFIIA/chemistry/*metabolism
;
Transcription Factor TFIID/chemistry/*metabolism
;
Transcription Factors/chemistry/*metabolism/ultrastructure
;
*Transcriptional Activation
Print ISSN:
0028-0836
Digitale ISSN:
1476-4687
Thema:
Biologie
,
Chemie und Pharmazie
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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