Transcription models

The cell cycle-modulated post-transcriptional model shown in Figure 5 is adequate to account for the results described for both synchronized and random populations of mammalian cells in culture. A recent report that actinomycin D stimulated the normally inducible synthesis of tyrosinase in Neurospora crassa (Horowitz et al., 1970) suggests that the type of regulation proposed in Figure 5 may extend to more primitive eukaryotic cells as well. The increasing number of reports that actinomycin D either stimulates the synthesis of certain specific proteins or else prevents their deinduction likewise strongly... 

Fig. 7. Transcription model for regulation of the ara OIBAD operon, including self catabolite repression.

Our discussion shows that the Ising model, lattice gas and binary alloy are related and present one and the same statistical mechanical problem. The solution to one provides, by means of the transcription tables, the solution to the others. Flistorically, however, they were developed independently before the analogy between the models was recognized. 

More than 30 years ago Jacob and Monod introduced the Escherichia coli lac operon as a model for gene regulation. The lac repressor molecule functions as a switch, regulated by inducer molecules, which controls the synthesis of enzymes necessary for E. coli to use lactose as an energy source. In the absence of lactose the repressor binds tightly to the operator DNA preventing the synthesis of these enzymes. Conversely when lactose is present, the repressor dissociates from the operator, allowing transcription of the operon. 

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. 

Figure 9.2 Schematic model for transcriptional activation. The TATA box-binding protein, which bends the DNA upon binding to the TATA box, binds to RNA polymerase and a number of associated proteins to form the preinitiation complex. This complex interacts with different specific transcription factors that bind to promoter proximal elements and enhancer elements.

A model called histone code theory includes more aspects of chromatin regulation which have been identified. The histone code theory predicts that histone acetylation and other posttranslational histone modifications serve as binding sites for regulatory proteins which mediate processes like gene transcription upon recruitment (see Fig. 2b) [3]. In this context histone modifications can be understood as... 

Thiazolidinediones (synonyms glitazones, insulin sensitizers rosiglitazone, pioglitazone) are a novel class of oral antidiabetic drugs that activate the transcription factor peroxisome proliferator-activated receptor (PPARy). Thiazolidinediones ameliorate insulin resistance in obese animal models and in individuals... 

Finally, it has to be mentioned that LPA also has an intracellular target site, which is the nuclear transcription factor, peroxisome proliferator-activated receptor-y (PPARy). LPA competes for thiazolidinedione binding and activates PPARy-dependent gene transcription. Thereby, LPA induced neointima formation in a rat carotid artery model. 

Fig. 3.14 Model for polyamide inhibition of the p55/p50 heterodimeric transcription factor NF-kB. Polyamides designed to target both the p65 and p50 DNA subsites (NF-kB site in bracket) demonstrated that only those targeting the p50 subsite effectively inhibit heterodimer binding. Symbols are defined in Fig. 3.4...

Upon binding, the artificial transcription factor recruits the necessary transcriptional machinery for gene activation. (Bottom, left) Ball-and-stick model for a polyamide conjugated to the VP2 activation domain. Symbols are as in Fig. 3.4. (Bottom, right) Structure of the polyamide-VP2 conjugate with the polyproline linker domain in brackets... 

Fig. 2. Modulation of the RseA activity a working model. In the absence of non-native proteins in the periplasm, is bound to the RseA anti-sigma factor this binding is stabilized by RseB, a co-anti-sigma factor, in the periplasm. Upon accumulation of non-native proteins within the periplasm, RseB is released followed by dissociation of which interacts with RNA polymerase core enzyme to initiate transcription of the heat shock genes of the sigma-E regulon...

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