Molecular transcription factor

Molecular Transcription Factor Activation in the Cell Nucleus... 

The general transcription factor TFllD is believed to be the key link between specific transcription factors and the general preinitiation complex. However, the purification and molecular characterization of TFllD from higher eucaryotes have been hampered by its instability and heterogeneity. All preparations of TFllD contain the TATA box-binding protein in combination with a variety of different proteins called TBP-associated factors, TAFs. When the preinitiation complex has been assembled, strand separation of the DNA duplex occurs at the transcription start site, and RNA polymerase II is released from the promoter to initiate transcription. However, TFIID can remain bound to the core promoter and support rapid reinitiation of transcription by recruiting another molecule of RNA polymerase. 

The two homologous repeats, each of 88 amino acids, at both ends of the TBP DNA-binding domain form two stmcturally very similar motifs. The two motifs each comprise an antiparallel p sheet of five strands and two helices (Figure 9.4). These two motifs are joined together by a short loop to make a 10-stranded p sheet which forms a saddle-shaped molecule. The loops that connect p strands 2 and 3 of each motif can be visualized as the stirmps of this molecular saddle. The underside of the saddle forms a concave surface built up by the central eight strands of the p sheet (see Figure 9.4a). Side chains from this side of the P sheet, as well as residues from the stirrups, form the DNA-binding site. No a helices are involved in the interaction area, in contrast to the situation in most other eucaryotic transcription factors (see below). 

Clock gene and transcription factor with histone acetyl-transferase (HAT) activity that (in complex with BMAL1) constitutes a positive limb of molecular circadian oscillators. 

In the case of liganded NRs, ligand binding is the first and ciucial molecular event that switches the function of these transcription factors from inactive to active state by inducing a conformational change in the LBD of the receptor (Fig. 1). This specific conformation allows the second step of NR activation that corresponds to the recruitment of coregulatoiy complexes, which contain chromatin-modifying enzymes required for transcription. The transcriptional coactivators are very diverse and have expanded to more than hundred in number. These include the pi 60 family of proteins,... 

Nakai, A., Morimoto, R.I. (1993). Characterization of a novel chicken heat shock transcription factor, heat shock factor 3, suggests a new regulatory pathway. Molecular Cellular Biology 13, 1983-1997. 

Romanelli A., Pedone C., Saviano M., Bianchi N., Borgatti M., Mischiati C., Gambari R. Molecular interactions between nuclear factor B (NF-kB) transcription factors and a PNADNA chimera mimicking NF-kB binding sites. Eur. J. Biochem. 2001 268 6066-6075. 

In summary, the apparent redox modulation of lycopene certainly affects two important redox sensitive transcription factors at higher concentrations of lycopene. However, electrophilic lycopene oxidation products cannot be ruled out as the major activators and the activation may be due to specific molecular interactions. 

Finally, the third level of molecular description can be illustrated by the complex formed between a transcription factor and the DNA molecule. In such a complex, the atoms involved in the interaction, the hydrogen bonds formed between the amino acids and the bases are shown, because this description, is necessary to explain the specificity of molecular recognition. 

Through these examples, I wanted to illustrate the fact that the expression molecular description can have at least three different meanings. These three levels of representation are not independent. For instance, the atoms and bonds that make up the jaws of RNA polymerase II can be described, as well as RNA polymerase II can be integrated, with transcription factors and DNA, in the general picture of the preinitiation transcription complex. However, in order to answer a specific question, one particular level of description is always more significant, better adapted than others, with a greater explanatory value. 

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