scholarly journals Perspectives on the RNA polymerase II core promoter

2006 ◽  
Vol 34 (6) ◽  
pp. 1047-1050 ◽  
Author(s):  
T. Juven-Gershon ◽  
J.-Y. Hsu ◽  
J.T. Kadonaga

The RNA polymerase II core promoter is a critical yet often overlooked component in the transcription process. The core promoter is defined as the stretch of DNA, which encompasses the RNA start site and is typically approx. 40–50 nt in length, that directs the initiation of gene transcription. In the past, it has been generally presumed that core promoters are general in function and that transcription initiation occurs via a common shared mechanism. Recent studies have revealed, however, that there is considerable diversity in core promoter structure and function. There are a number of DNA elements that contribute to core promoter activity, and the specific properties of a given core promoter are dictated by the presence or absence of these core promoter motifs. The known core promoter elements include the TATA box, Inr (initiator), BREu {BRE [TFIIB (transcription factor for RNA polymerase IIB) recognition element] upstream of the TATA box} and BREd (BRE downstream of the TATA box), MTE (motif ten element), DCE (downstream core element) and DPE (downstream core promoter element). In this paper, we will provide some perspectives on current and future issues that pertain to the RNA polymerase II core promoter.

2006 ◽  
Vol 73 ◽  
pp. 225-236 ◽  
Author(s):  
Petra Gross ◽  
Thomas Oelgeschläger

The initiation of mRNA synthesis in eukaryotic cells is a complex and highly regulated process that requires the assembly of general transcription factors and RNAP II (RNA polymerase II; also abbreviated as Pol II) into a pre-initiation complex at the core promoter. The core promoter is defined as the minimal DNA region that is sufficient to direct low levels of activator-independent (basal) transcription by RNAP II in vitro. The core promoter typically extends approx. 40 bp up- and down-stream of the start site of transcription and can contain several distinct core promoter sequence elements. Core promoters in higher eukaryotes are highly diverse in structure, and each core promoter sequence element is only found in a subset of genes. So far, only TATA box and INR (initiator) element have been shown to be capable of directing accurate RNAP II transcription initiation independent of other core promoter elements. Computational analysis of metazoan genomes suggests that the prevalence of the TATA box has been overestimated in the past and that the majority of human genes are TATA-less. While TATA-mediated transcription initiation has been studied in great detail and is very well understood, very little is known about the factors and mechanisms involved in the function of the INR and other core promoter elements. Here we summarize our current understanding of the factors and mechanisms involved in core promoter-selective transcription and discuss possible pathways through which diversity in core promoter architecture might contribute to combinatorial gene regulation in metazoan cells.


2017 ◽  
Author(s):  
Kapil Gupta ◽  
Aleksandra A. Watson ◽  
Tiago Baptista ◽  
Elisabeth Scheer ◽  
Anna L. Chambers ◽  
...  

AbstractGeneral transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). TBP binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by TBP and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for TBP binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box mimicry. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/TBP complex, revealing TAF11/TAF13 interaction with the DNA binding surface of TBP. We identify a highly conserved C-terminal TBP-binding domain (CTID) in TAF13 which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.


2011 ◽  
Vol 100 (3) ◽  
pp. 65a
Author(s):  
Alexandros Pertsinidis ◽  
Sang Ryul Park ◽  
Robert Coleman ◽  
Andrei Revyakin ◽  
Robert Tjian ◽  
...  

2020 ◽  
Vol 9 ◽  
Author(s):  
Daniel Reines

More than 50 years after the identification of RNA polymerase II, the enzyme responsible for the transcription of most eukaryotic genes, studies have continued to reveal fresh aspects of its structure and regulation. New technologies, coupled with years of development of a vast catalog of RNA polymerase II accessory proteins and activities, have led to new revelations about the transcription process. The maturation of cryo-electron microscopy as a tool for unraveling the detailed structure of large molecular machines has provided numerous structures of the enzyme and its accessory factors. Advances in biophysical methods have enabled the observation of a single polymerase’s behavior, distinct from work on aggregate population averages. Other recent work has revealed new properties and activities of the general initiation factors that RNA polymerase II employs to accurately initiate transcription, as well as chromatin proteins that control RNA polymerase II’s firing frequency, and elongation factors that facilitate the enzyme’s departure from the promoter and which control sequential steps and obstacles that must be navigated by elongating RNA polymerase II. There has also been a growing appreciation of the physical properties conferred upon many of these proteins by regions of each polypeptide that are of low primary sequence complexity and that are often intrinsically disordered. This peculiar feature of a surprisingly large number of proteins enables a disordered region of the protein to morph into a stable structure and creates an opportunity for pathway participants to dynamically partition into subcompartments of the nucleus. These subcompartments host designated portions of the chemical reactions that lead to mRNA synthesis. This article highlights a selection of recent findings that reveal some of the resolved workings of RNA polymerase II and its ensemble of supporting factors.


1995 ◽  
Vol 15 (2) ◽  
pp. 1049-1059 ◽  
Author(s):  
C P George ◽  
L M Lira-DeVito ◽  
S L Wampler ◽  
J T Kadonaga

To explore the diversity in the mechanisms of basal transcription by RNA polymerase II, we have employed a novel biochemical approach that involves perturbation of the transcription reaction with exogenously added TFIIB or TATA box-binding protein (TBP). Under these conditions, we observe promoter-selective inhibition of transcription by excess TFIIB or excess TBP. This inhibition occurs at the level of basal transcription, because it is observed with minimal promoters that comprise only the TATA box and initiation site sequences as well as with preparations of basal transcription factors that have been purified to greater than 90% homogeneity. In addition, the excess basal factors inhibit the assembly of a functional preinitiation complex but do not inhibit transcription initiation from preassembled preinitiation complexes. A study of several promoters revealed a reciprocal trend in the promoter specificity of inhibition by excess TFIIB versus that by excess TBP. At opposite ends of this spectrum, promoters are strongly inhibited by excess TFIIB but not excess TBP and vice versa. These results reveal the existence of a spectrum of mechanisms for preinitiation complex assembly at different promoters. The mechanistic preference appears to be specified by the aggregate of basal promoter elements rather than by an individual component, such as the TATA box or initiation site sequence. This spectrum provides a new parameter by which differences in the function of minimal class II promoters can be analyzed in the context of both basal and regulated transcription.


eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Kapil Gupta ◽  
Aleksandra A Watson ◽  
Tiago Baptista ◽  
Elisabeth Scheer ◽  
Anna L Chambers ◽  
...  

General transcription factor TFIID is a key component of RNA polymerase II transcription initiation. Human TFIID is a megadalton-sized complex comprising TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs). TBP binds to core promoter DNA, recognizing the TATA-box. We identified a ternary complex formed by TBP and the histone fold (HF) domain-containing TFIID subunits TAF11 and TAF13. We demonstrate that TAF11/TAF13 competes for TBP binding with TATA-box DNA, and also with the N-terminal domain of TAF1 previously implicated in TATA-box mimicry. In an integrative approach combining crystal coordinates, biochemical analyses and data from cross-linking mass-spectrometry (CLMS), we determine the architecture of the TAF11/TAF13/TBP complex, revealing TAF11/TAF13 interaction with the DNA binding surface of TBP. We identify a highly conserved C-terminal TBP-interaction domain (CTID) in TAF13, which is essential for supporting cell growth. Our results thus have implications for cellular TFIID assembly and suggest a novel regulatory state for TFIID function.


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