Transcription factor binding to DNA

Families of zinc[Pg.191]

To influence the activity of RNA polymerase, transcription factors bind to DNA at enhancer sites and/or promoter sites. Four different structures of these factors are known. They possess structures that allow specific binding to DNA. They are given names that indicate the key protein domains that encourage this binding, as follows ... 

Odom DT, Parker CS, Barton JK. Site-specific inhibition of transcription factor binding to DNA by a metallointercalator. Biochemistry 1999 38 5155-63. 

Transcription factors bind to DNA through regions referred to as DNA-binding regions, or motifs they are highly conserved between species. There are four major structural motifs ... 

Protein-protein interactions are a critical part of protein-DNA binding. Many specific transcription factors bind to DNA as homodimers or heterodimers. The cooperativity introduced by the dimer structure strengthens the binding and improves the ability to regulate gene transcription by regulating the activity of these transcription factors. 

The mechanisms by which these determinants modulate transcription are not clearly understood, but most data suggest that they may interfere directly or indirectly with transcription-factor binding to DNA response elements. It is likely that chromatin structure and DNA methylation play major roles in establishing gene-expression patterns during cell development. 

Figure 10.28 Schematic diagram of the binding of the transcription factor Max to DNA. The two monomers of Max (blue and green) form a dimer through both the helix-loop-helLx regions which form a four-helix bundle like MyoD, and the zipper regions, which are arranged in a coiled coil. The N-terminal basic regions bind to DNA in a way similar to GCN4 and MyoD. (Adapted from A.R. Ferre-D Amare et al., Nature 363 38-4S, 1993.)...

Figure 12.4 Model for SV40 enhancer-mediated sequence-specific plasmid nuclear import. (A) Cartoon of the SV40 origin region, containing two copies of the 72 bp enhancer repeats. As can be seen, multiple transcription factors have been identified to bind to this region (only a few proteins are listed). (B) Model for nuclear import. Newly synthesized NLS-containing transcription factors bind to the SV40 enhancer in the cytoplasm to form a protein-DNA complex. Importin family members can recognize the DNA-bound NLSs to facilitate the nuclear import of the complex.

An important eukaryotic transcription factor is the nuclear factor, NF-kB (NF-xB). This factor binds to DNA through i-sheets. The i-sheets of the dimeric transcription factor wrap around the DNA like a mantle. Contacts are made, as in the case of a-helices, with die major groove of the DNA. The structure is shown in Plate 18. 

Camp response element binding proteins, as transcription factors, bind to certain sequences called camp response elements (CRE) in DNA and thereby increase or decrease the transcription of certain genes... 

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