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Structural visualization of key steps in human transcription initiation
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Structural visualization of key steps in human transcription initiation
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Journal Article
Structural visualization of key steps in human transcription initiation
2013
Overview
Eukaryotic transcription initiation requires the assembly of general transcription factors into a pre-initiation complex that ensures the accurate loading of RNA polymerase II (Pol II) at the transcription start site. The molecular mechanism and function of this assembly have remained elusive due to lack of structural information. Here we have used an
in vitro
reconstituted system to study the stepwise assembly of human TBP, TFIIA, TFIIB, Pol II, TFIIF, TFIIE and TFIIH onto promoter DNA using cryo-electron microscopy. Our structural analyses provide pseudo-atomic models at various stages of transcription initiation that illuminate critical molecular interactions, including how TFIIF engages Pol II and promoter DNA to stabilize both the closed pre-initiation complex and the open-promoter complex, and to regulate start--initiation complexes, combined with the localization of the TFIIH helicases XPD and XPB, support a DNA translocation model of XPB and explain its essential role in promoter opening.
Cryo-electron microscopy structures of key intermediates during the sequential assembly of the pre-initiation complex are presented; structures of the closed and open-promoter complexes allow insights into the process of promoter melting.
First steps in DNA to RNA transcription
The basal transcriptional machinery includes RNA polymerase II and several general transcription factors which assemble into a pre-initiation complex (PIC) on promoter DNA. Here, Eva Nogales and colleagues present cryo-EM structures of key intermediates produced during the sequential assembly of the PIC. Structures of the closed and open promoter complexes allow insights into the process of promoter melting.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ DNA
/ Enzymes
/ Humanities and Social Sciences
/ Humans
/ Methods
/ Promoter Regions, Genetic - genetics
/ Proteins
/ RNA Polymerase II - chemistry
/ RNA Polymerase II - metabolism
/ RNA Polymerase II - ultrastructure
/ Science
/ TATA-Box Binding Protein - chemistry
/ TATA-Box Binding Protein - metabolism
/ Transcription Factor TFIIH - chemistry
/ Transcription Factor TFIIH - metabolism
/ Transcription Factors, TFII - chemistry
/ Transcription Factors, TFII - metabolism
/ Transcription Factors, TFII - ultrastructure
