Key Concepts of Section 9.4

• Expression of eukaryotic protein-coding genes is generally regulated through multiple protein-binding transcription-control regions that are located close to or distant from the transcription start site (see Figure 9-23).

• Promoters direct binding of RNA polymerase II to DNA, determine the site of transcription initiation, and influence the frequency of transcription initiation.

• Promoter-proximal elements occur within about 200 bp of a start site. Several such elements, containing 6–10 bp, may help regulate a particular gene.

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  Enhancers, which contain multiple short control elements, may be located from 200 bp to tens of kilobases upstream or downstream from a promoter, within an intron, or downstream from the final exon of a gene.

• Promoter-proximal elements and enhancers are often cell-type-specific, functioning only in specific differentiated cell types.

• Transcription factors, which activate or repress transcription, bind to promoter-proximal regulatory elements and enhancers in eukaryotic DNA.

• Transcription activators and repressors are generally modular proteins containing a single DNA-binding domain and one or a few activation domains (for activators) or repression domains (for repressors). The different domains are frequently linked by flexible, intrinsically disordered polypeptide regions (see Figure 9-28).

• Among the most common structural motifs found in the DNA-binding domains of eukaryotic transcription factors are the homeodomain, C2H2 zinc finger, basic zipper (leucine zipper), and basic helix-loop-helix (bHLH). All these and many other DNA-binding motifs contain one or more α helices that interact with the major groove in their cognate site in DNA.

• Activation and repression domains in transcription factors exhibit a variety of amino acid sequences and three-dimensional structures. In general, these functional domains interact with co-activators or co-repressors, which are critical to the ability of transcription factors to modulate gene expression.

• The transcription-control regions of most genes contain binding sites for multiple transcription factors. Transcription of such genes varies depending on the particular repertoire of transcription factors that are expressed and activated in a particular cell at a particular time.

• Combinatorial complexity in transcriptional control results from alternative combinations of monomers that form heterodimeric transcription factors (see Figure 9-32) and from cooperative binding of transcription factors to composite control sites (see Figure 9-33).

• Binding of multiple transcription factors to multiple sites in an enhancer forms a DNA-protein complex called an enhanceosome (see Figure 9-34).