Regulation of transcription in eukaryotes

Transcription and transcriptional regulation is more complicated in eukaryotes than in prokaryotes. The very much larger amount of DNA in eukaryotes is organized with histones 

5 -[enhanc.er] [intervening DNA] [further control elements]—[TATA box]- 

As indicated in Chapters 5, 7 and 8, transcription can be switched on by a variety of signalling pathways. Thus, cAMP-mediated pathways generate phosphorylated CREB proteins that activate expression of particular proteins by binding to promoters called cAMP response elements (GREs). Similarly, Ca2+-dependent PKC activation results in phosphorylation of transcription factors that bind to and activate tetradecanoylphorbol ester response element (TRE) promoters. In the immune response bacterial lipopolysaccharide (LPS) and particular cytokines can switch on signalling pathways resulting in activation of transcription factors such as NFkB (Chapter 7) with resultant expression of proteins such as cytokines, 

COX-2 and iNOS. Some steroid hormone receptors complexed with their specific hormone ligand act as DNA-binding transactivators to switch on transcription of particular genes. However, in the hormone-free state these proteins can act as repressors and block initiation of transcription of these genes. DNA and associated transcription, translation and replication processes are similar in plants and non-plant eukaryotes. Nevertheless, some plants elaborate DNA binding compounds or compounds that otherwise interfere with gene expression and DNA replication (Tables 9.1—9.4). 

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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. 

How does the regulation of transcription in eukaryotes differ from that in bacteria ... 

Further details of the nature and regulation of transcription in prokaryotes and eukaryotes and the post-transcriptional processing of mRNA transcripts are given in Chapter 9. 

In prokaryotes, mRNA synthesis can be controlled simply by regulating initiation of transcription. In eukaryotes, mRNA is formed from a primary transcript followed by a series of processing events (e.g., intron excision, polyadenylylation). Eukaryotes regulate not only transcription initiation but the various stages of processing as well. 

Regulation of transcription is a central mechanism by which cells respond to developmental and environmental cues. RNA polymerase Il-mediated transcription in eukaryotes is to a large extent regulated at the level of chromatin, which forms a physical barrier for the binding of proteins to the promoter region of a target gene. The basic unit of chromatin is the nucleosome, which consists of an octamer of histone proteins around which the DNA is wrapped (see Fig. la). 

Protein methylation is one of the most common protein modifications found in a wide range of prokaryotic and eukaryotic proteins that are involved either in regulation of transcription or in translation. Several amino acids can be modified, mainly by either N-methylation or C-methylation. Protein methylation has been... 

Transcription in eukaryotes an overview (G5) Transcription of protein-coding genes in eukaryotes (G6) Regulation of transcription by RNA Pol II (G7)... 

The translation of mRNA to protein concludes the gene expression cascade and links the proteome to the genome. Consequently, control of translation can be a direct and effective means to modulate the proteome [21, 30, 31]. In addition to transcript interactions with protein regulators, translation is also modulated by structural features or regulatory sequences appearing within the mRNA molecules. The 7-methylguanylate triphosphate nucleotidyl caps at the 5 end, poly-A tails, uORFs, and IRESs are examples of structures that affect the rate and efficiency of translation in eukaryotes [21]. 

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). 

Cyclins and Cdks are conserved among all multicellular eukaryotes. Regulation of transcription of genes encoding components of the cell-cycle machine by cyclin-Cdks, in cooperation with the E2F transcription factors, are, in principle, the same in vertebrates and invertebrates. Furthermore, at least one of the two families of Cdk inhibitors in vertebrates is also present in Drosophila. 

We then turn to transcription in eukaryotes, beginning with promoter structure and the transcription-factor proteins that regulate promoter activity. A distinctive feature of eukaryotic DNA templates is the presence of enhancer sequences that... 

However, synthesis of mRNA in eukaryotes is not a simple matter of initiation at a promoter, as it is in prokaryotes, but includes several steps in which the primary transcript is converted to mRNA (Chapter 25). Control of these processing steps is also used to regulate gene expression in eukaryotes. 

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... 

Transcriptional control is the primary means of regulating gene expression in eukaryotes, as it is in bacteria. 

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