Transcription factors and DNAbinding domains

Transcription factors, whether bound to enhancers or to promoter-proximal elements, need to perform at least two functions: (1) DNA binding and (2) transcription activation or repression. For this reason, they are usually

10.6 Transcriptional regulation in eukaryotes

Promoter Proximal Elements

Figure 10-24 Regulation of RNA polymerase II by promoter-proximal elements.

(a) DNA forms a loop to bring together an enhancer and promoter-proximal elements. Their interaction with RNA polymerase II initiates transcription. (b) Interaction of the DNA-bending protein with DNA. [Part a after B. Turner, Chromatin and Gene Regulation. Blackwell Science, 2001.]

Figure 10-24 Regulation of RNA polymerase II by promoter-proximal elements.

(a) DNA forms a loop to bring together an enhancer and promoter-proximal elements. Their interaction with RNA polymerase II initiates transcription. (b) Interaction of the DNA-bending protein with DNA. [Part a after B. Turner, Chromatin and Gene Regulation. Blackwell Science, 2001.]

composed of at least two domains, one that binds DNA and another that influences transcription by binding to another bound protein. For example, a transcription factor might have the DNA-binding domain at its amino end and the activation domain at its carboxyl end.

A few characteristic DNA-binding domains have been given descriptive names such as helix-turn-helix, zinc finger, helix-loop-helix, and leucine zipper. The helix-turn-helix domain is the best studied and is found in both prokaryotic and eukaryotic regulatory proteins. As the name indicates, it consists of at least two a helices. Most DNA-binding domains are positively charged so that they are attracted to the negatively charged DNA phosphate backbone. When they get close to the DNA, hydrogen bonding between the bases and amino acids fine-tunes the interaction. Binding domains usually fit into the major groove of the double helix. Figure 10-25 shows how the helix-turn-helix domain interacts with DNA.

DNA-binding domains are conserved from yeast to plants to humans. Recall from the discussion of molec-

Helix Turn Helix

a helice

Figure 10-25 Interaction of helix-turn-helix binding domain with DNA.

a helice

Figure 10-25 Interaction of helix-turn-helix binding domain with DNA.

ular mimicry that proteins are extremely versatile molecules that can assume a wide range of shapes and charged surfaces. In this case, a few protein domains that were able to fit snugly into the DNA double helix evolved in early life forms and have been used over and over again for a variety of functions. Thus, because of the modular construction of transcripton factors, the same DNA-binding domain in two organisms may be part of transcription factors with very different regulatory roles.

MESSAGE The structures of DNA-binding proteins enables them to contact specific DNA sequences through polypeptide domains that fit into the major groove of the DNA double helix.

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