As mentioned earlier, there is a large number of specialized transcription factors identified. Although there is significant variation in the structures of these factors, they all share a single property: they have two functional domains or regions.

• There is a DNA-binding domain, which recognizes the specific DNA sequence of the enhancer, and binds to it.
• There is a transactivation domain, which interacts with other proteins and thereby increases the rate of transcription.

Transcription factors can be classified according to the structure of their DNA binding domain, of which there are five basic types:

• Zinc finger proteins: these proteins have a peptide sequence that includes two cysteines and two histidines at specific locations in the polypeptide. These amino acids are crosslinked by zinc, producing a loop, or 'finger' structure, which binds to DNA. Zinc fingers are usually found in pairs, although proteins can have a variable number of fingers in a single polypeptide. (As many as 30 zinc fingers have been identified in one polypeptide.)
• Helix-turn-helix proteins: these proteins contain three alpha helices (for a description of alpha helices, see the module on protein structure) joined by curved stretches of polypeptide sequence. The most important type of helix-turn-helix motif is the homeodomain, which is the DNA binding domain of a family of developmentally important transcription factors.
• Leucine zipper proteins: in order to bind DNA, these polypeptides need to dimerize (that is, join together to form a pair). They dimerize by means of the leucine zipper, which is an alpha helix containing a leucine in every other turn of the helix. The leucine zipper on one polypeptide interacts with the leucine zipper on another polypeptide, joining the two polypeptides together in a mechanism reminiscent of the 'zipping up' of a zipper (hence the name). Binding to DNA is accomplished via an adjacent region of basic (positively charged) amino acids.
• Helix-loop-helix proteins: not to be confused with the helix-turn-helix proteins, these proteins, like the leucine zipper proteins, need to dimerize in order to bind DNA. They dimerize via their helix-loop-helix domain, which (as the name implies) consists of two alpha helices (there are only two here, compared to three in the helix-turn-helix proteins) joined by a polypeptide loop. DNA binding is also often accomplished using an adjacent stretch of basic amino acids, which binds to the negatively charged DNA.
• Steroid receptors: these were discussed earlier, and are mentioned here to contrast them with the other groups of transcription factors. Steroid receptors have a third functional domain in addition to the two shared by all transcription factors: they have a steroid-binding domain, through which they bind their ligand, and have their activity regulated.

Eukaryotic Gene Regulation: Summary of Key Points

• Eukaryotic gene expression can be regulated at a variety of points along the pathway of gene expression, including transcription, processing, mRNA stability, and translation.
• Some RNA molecules can be undergo differential splicing, producing different mRNA molecules encoding slightly different polypeptides.
• Full, correct transcription requires the concerted activity of a promoter and at least one enhancer. Enhancers increase transcription of a gene over basal level, and are responsible for tissue-specific gene transcription.
• Enhancers are bound by specialized transcription factors; when the factors bind to enhancers, they enhance transcription.
• Transcription factor activity in a cell can be regulated by whether or not the factor is synthesized, by environmental signals, and by signals (such as hormones) from other cells.
• Transcription factors have one functional domain for DNA binding, and one for transcription activation. Transcription factors can be classified according to the structure of their DNA binding domains; these include zinc finger proteins, helix-turn-helix proteins, leucine zipper proteins, helix-loop-helix proteins, and steroid receptors.