Transcription factors recognition sequences

Kim, J., Klooster, S., Shapiro, D. J. (1995) Intrinsically bent DNA in a eukaryotic transcription factor recognition sequence potentiates transcription activation. J Biol Chem 270, 1282-1288. 

H8. Haugen, A., Mann, D., Murray, C., Weston, A., and Willey, J. C. lnterleukin-1 alpha gene intron containing variable repeat region coding for the SPl transcription factor recognition sequence is polymorphic. Mol. Carcinog. 2, 68-71 (1989). 

Figure 9.12 Schematic diagram of the structure of the heterodimeric yeast transcription factor Mat a2-Mat al bound to DNA. Both Mat o2 and Mat al are homeodomains containing the helix-turn-helix motif. The first helix in this motif is colored blue and the second, the recognition helix, is red. (a) The assumed structure of the Mat al homeodomain in the absence of DNA, based on Its sequence similarity to other homeodomains of known structure, (b) The structure of the Mat o2 homeodomain. The C-terminal tail (dotted) is flexible in the monomer and has no defined structure, (c) The structure of the Mat a 1-Mat a2-DNA complex. The C-terminal domain of Mat a2 (yellow) folds into an a helix (4) in the complex and interacts with the first two helices of Mat a2, to form a heterodimer that binds to DNA. (Adapted from B.J. Andrews and M.S. Donoviel, Science 270 251-253, 1995.)...

A sequence stretch 300 base pairs upstream of the transcriptional start site suffices for most of the transcriptional regulation of the IL-6 gene (Fig. 1). Within this sequence stretch several transcription factors find their specific recognition sites. In 5 to 3 direction, AP-1, CREB, C/EBP 3/NF-IL6, SP-1 and NF-kB can bind to the promoter followed by TATA and its TATA binding protein TBP. Most enhancer factors become active in response to one or several different stimuli and the active factors can trigger transcription individually or in concert. For example, AP-1 is active upon cellular stress, or upon stimuli that tell cells to proliferate CREB becomes also active if cells experience growth signals, but also upon elevation of intracellular levels of cyclic adenosine monophosphate (cAMP), which occurs upon stimulation if so called hormone-activated G protein-coupled receptors. 

The zinc fingers are common structures among the transcription factors. Nevertheless, the coordination with zinc is more frequently produced between two histidine residues and two neighboring cysteines than when it is among four cysteine residues, as occurs in the nuclear hormone receptors. The zinc fingers provide an optimum architecture for the mutual recognition between specific sequences of amino acids and nucleotides. In the case of the nuclear receptors, the interaction occurs between particular amino acids of the DBD and guanine residues of the DNA sequence (Fig. 1.7). 

The first zinc binding motif discovered was that of the eucaryotic transcription factor TFIIIA of Xenopus laevis which contains 9 copies of a Cys2His2-Zinc motif The structure of the binding motif is shown in Fig. 1.4. The central zinc ion serves to pack an a-hehx against a P-sheet and thereby position the a-helix. The recognition of the DNA sequence occurs via this a-helix. 

Fig. 1.10. The eucaryotic transcription factor NFxB in complex with DNA. Shown is the structure of a fragment of the p50 subunit of NFxB complexed with the recognition sequence. p50 of NFxB binds DNA as a dimer. Each of the subunits contains a bundle of P-sheets which envelops the DNA so that only the minor groove is exposed. After Ghosh et al. (1995), with permission.

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