Transcriptional control in eukaryotes can be accomplished at several levels. Chromatin structure can control transcription. The formation of so-called hypersensitive sites (sites where the DNA is not bound into nucleosomes) allows protein factors and RNA polymerase to access the DNA. This is necessary for transcription to occur, but hypersensitive sites are not enough. The removal of histone H1 allows transcription to occur from a chromatin domain. Some protein factors (for example, TBF) may be bound to a promoter region even if the gene is not being transcribed. TBF also is necessary but not sufficient for transcription.
Transcription control factors promote or prevent RNA polymerase binding. Various trans-acting factors (proteins) bind at specific cis-acting sequences. These factors can bind upstream of the promoter. Other factors bind to enhancer sequences and the chromatin folds to allow the enhancer-binding factors to bind to the proteins at the promoter region or at the upstream sequences. Protein-protein interactions between bound factors contribute to transcriptional activation. Developmental gene regulation can occur through protein factors—for example, by the presence of protein at different positions in the embryo.
DNA binding proteins have common structures and means of recognizing DNA sequence. The specificity of the interaction depends on the amino acids in the protein that are available to encounter specific structures in DNA sequences. For example, the amido group on glutamine or asparagine may provide a hydrogen-bond donor to the Oxygen at position 6 of guanosine. See Figure 1 .
Two common DNA-binding structures are found in a variety of transcriptional control proteins. The helix-turn-helix motif allows interaction with DNA sequences. The two α-helices are positioned at an angle to each other. One α-helix (the binding helix) contacts the major groove of the DNA molecule. The other α-helix positions the binding helix relative to the DNA. Transcriptional control proteins can have other domains that allow their interaction with other transcription factors; these protein-protein interactions allow multiple binding events to occur. Helix-turn-helix proteins are found in both prokaryotic and eukaryotic systems. See Figure 2 .
Zinc-fingers are common in DNA-binding proteins of eukaryotes but are not found in prokaryotes. Examples of zinc-finger proteins include the RNA polymerase III transcription factor TFIIIA, steroid receptors, and some gene products that control development. The zinc-finger consists of pairs of cysteine and/or histidine residues within an α-helix. These residues bind tightly to a Zn2 ion, which allows the α-helical amino acids to interact with specific sequences. See Figure 3 .
Again, protein-protein contacts allow for specific interaction between different proteins. These contacts are hypothesized to occur by the interaction of hydrophobic domains sometimes called “leucine zippers” to denote their amino acid composition as well as their function.
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