Regulation of transcription initiation

This chapter focuses primarily on the regulation of transcription initiation, although aspects of posttranscriptional and translational regulation are also described. Of the regulatory processes illustrated in Figure 28-1, those operating at the level of transcription initiation are the best documented and probably the most... 

RNA polymerases bind to DNA and initiate transcription at promoters (see Fig. 26-5), sites generally found near points at which RNA synthesis begins on the DNA template. The regulation of transcription initiation often entails changes in how RNA polymerase interacts with a promoter. 

M. M. Barker, T. Gaal and R. L. Course (2001). Mechanism of regulation of transcription initiation by ppGpp. II. Models for positive control based on properties of RNAP mutants and competition for RNAP. J. Mol. Biol., 305, 689-702. 

Direct measurements of the transcription rates of multiple genes in different cell types have shown that regulation of transcription Initiation is the most widespread form of gene control in eukaryotes, as it is in bacteria. Nascent-chain analysis is a common method for determining the relative rates of transcription of different genes in cultured cells. In this method, also called run-on transcription analysis, Isolated nuclei are incubated with P-labeled ribonucleoside triphosphates for a brief time (e.g., 5 minutes or less). During... 

Overall, histone acetylation and deacetylation represents an important tool with which transcription can be positively or negatively influenced. The nucleosomes and, in a further sense, chromatin structure assiune a central role in the regulation of transcription. Nucleosome structure and nucleosome position can decisively contribute to the accessibility of DNA elements for transcription factors. The nucleosomes function as a framework that determines the spatial arrangement of a region of the DNA. Tlie nucleosome constellation must be modified during transcription initiation, whereby the post-translational modification of histones in the form of acetylation or deacetylation plays a significant role. The participation of other non-histone proteins remains an open issue and it is also imclear how a constitutive and permanent inactivation of a section of DNA can be accomplished via the chromatin structure. 

Control of transcription initiation permits the synchronized regulation of multiple genes encoding products with interdependent activities. For example, when their DNA is heavily damaged, bacterial cells require a coordinated increase in the levels of the many DNA repair enzymes. And perhaps the most sophisticated form... 

Despite this elaborate binding complex, repression is not absolute. Binding of the Lac repressor reduces the rate of transcription initiation by a factor of 10s. If the 02 and 03 sites are eliminated by deletion or mutation, the binding of repressor to CL alone reduces transcription by a factor of about 102. Even in the repressed state, each cell has a few molecules of /3-galactosidase and galactoside permease, presumably synthesized on the rare occasions when the repressor transiently dissociates from the operators. This basal level of transcription is essential to operon regulation. 

The expression of genes is regulated by processes that affect the rates at which gene products are synthesized and degraded. Much of this regulation occurs at the level of transcription initiation, mediated by regulatory proteins that either repress transcription... 

Initiation of transcription is a crucial regulation point for both prokaryotic and eukaryotic gene expression. Although some of the same regulatory mechanisms are used in both systems, there is a fundamental difference in the regulation of transcription in eukaryotes and bacteria. 

Enzymes That Catalyze Amino Acid Biosynthesis Are Regulated at the Level of Transcription Initiation The trp Operon Is Also Regulated after the Initiation Point for Transcription Genes for Ribosomes Are Coordinately Regulated Control of rRNA and tRNA Synthesis by the rel Gene... 

Enzymes That Catalyze Amino Acid Biosynthesis Are Regulated at the Level of Transcription Initiation... 

Gene expression in eukaryotes is usually regulated at the level of transcription initiation by a complex of RNA polymerase and an array of regulatory proteins that bind in and around the DNA promoter. 

Fig. 1. Control regions that regulate transcription of a typical eukaryotic protein-coding gene. Although shown as distinct entities here for clarity, in vivo the different regulatory proteins bound to the control elements and distant enhancers interact with each other and with the general transcription factors of the transcription initiation complex to modulate the rate of transcriptional initiation.

Translation can be inhibited through the phosphorylation of eukaryote initiation factor 2 (eIF2) by dsRNA-dependent PK (activated by viral dsRNA as a consequence of viral infection), by hemin-inhibited PK (activated in the absence of hemin in reticulocytes) and by GCN2 kinase (general control non-derepressible kinase) (activated by amino acid starvation and excess free tRNA). Phosphorylation of RNA polymerase II is a key process in the regulation of transcription (Chapter 9). 

Babitzke P. Regulation of transcription attenuation and translation initiation by allosteric control of an RNA-binding protein the Bacillus subtilis TRAP protein. Curr. Opin. Microbiol. 2004 7 132-139. 

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