Transcription activator

Steitz has suggested that DNA bending by CAP could contribute to activation of transcription by looping the DNA around CAP to provide for contacts between RNA polymerase and DNA upstream of the CAP-binding site. Such a model could explain how CAP can activate transcription from a variety of distances from the RNA polymerase-binding site since the size of the loop could vary. 

The polypeptide chains of the specific transcription factors usually have two different functions one is to bind to a specific DNA sequence and another is to activate transcription. These two functions are often... 

Lac repressor binds to both the major and minor grooves inducing a sharp bend in the DNA CAP-induced DNA bending could activate transcription Conclusion Selected readings... 

Once the TLRs have bound their respective ligand they initiate a signalling cascade to alert the host to the presence of a threat. This signal begins with specific adapter proteins and leads to the activation of transcription factors such as NFkB, ERF-3 and IRF-7 as shown in Fig. 1. These activated transcription factors cause changes in gene expression typically leading to the production of cytokines. 

Instead of activating transcription the cortisol-induced GR represses IL-6 synthesis and, even more surprisingly, repression does not involve the GRE elements, but rather the kB site (Fig. 1). It appeals that of a monomeric GR protein without itself touching the DNA interacts with the RelA component of NF-kB [3]. As a result GR blocks the action of NF-kB. The negative interference by this crosstalk is not restricted to NF-kB, it occurs also with AP-1 and CREB, and with several other transcription factors not relevant for IL-6 expression. A nuclear isoform of the LIM protein Trip6 mediates the interaction between these factors and is required for the inhibitory GR function. This interesting negative crosstalk is part of the immune-suppressive action of cortisol. 

Watowich, S., Morimoto, R.I., Lamb, R.A. (1991). Flux of the paramyxovirus hemagglutinin-neuraminidase glycoprotein through the endoplasmic reticulum activates transcription of the grp78-Bip gene. J. Virol. 65, 3690-3697. 

Xu, C. (1993). cDNA cloning of a mouse factor that activates transcription from a metal response element of the mouse metallothionein-1 gene in yeast. DNA Cell Biol. 12, 517-525. 

Figure 37-10. Two models for assembly of the active transcription complex and for how activators and coactivators might enhance transcription. Shown here as a small oval is TBP, which contains TFIID, a large oval that contains all the components of the basal transcription complex illustrated in Figure 37-9 (ie, RNAPII andTFIIA,TFIIB, TFIIE,TFIIF, and TFIIFI). Panel A The basal transcription complex is assembled on the promoter after the TBP subunit of TFIID is bound to the TATA box. Several TAFs (coactivators) are associated with TBP. In this example, a transcription activator, CTF, is shown bound to the CAAT box, forming a loop complex by interacting with a TAF bound to TBP. Panel B The recruitment model. The transcription activator CTF binds to the CAAT box and interacts with a coactivator (TAF in this case). This allows for an interaction with the preformed TBP-basal transcription complex. TBP can now bind to the TATA box, and the assembled complex is fully active.

DNA binding could result in a general conformational change that allows the bound protein to activate transcription, or these two functions could be served by separate and independent domains. Domain swap experiments suggest that the latter is the case. 

BRAND K, PAGE S, ROGLER G, BARTSCH A, BRANDL R, KNUECHEL R, PAGE M, KALTSCHMIDT C, BAEUERLE P A and NEUMEIER D (1996) Activated transcription factor NF-kB is present in the atherioscleotic lesion Journal Clinical Investigation 97, 1715-22. 

England, B. P., Heberlein, U., and Tjian, R. (1990). Purified Drosophila transcription factor, Adh distal factor-1 (Adf-1), binds to sites in several Drosophila promoters and activates transcription. J. Biol. Chem. 265 5086-5093. 

Figure 5.5. A. Schematic illustration of the E. coli RNA polymerase showing the domain structure of the a subunit. The cx-NTD domain is responsible for assembly of RNAP while the a-CTD domain binds DNA and is a target for transcriptional activators. B. The two-hybrid system is based on the interaction of proteins that are fused to the X repressor and NTD domain of the a subunit of RNAP. In the example shown, Gal4 interacts with Gall IP to recruit RNAP to the promoter and activate transcription of the lacZ reporter gene. Figure adapted from Dove and Hochschild (1998).

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