The Logic of Gene Transcription

Gene transcription begins with RNA polymerase binding to the promoter site, a short sequence about 25 nucleotides upstream of a gene's transcription start site. Sites like those labeled TATA and CAAT (Figure 4-6A) are found in about the same location flanking most eukaryotic genes. The rate of transcription is modified by the binding to enhancer sequence elements by DNA-binding proteins known as

chromatin remodeling compex TAFs

Figure 4-7. Basic cis-regulation of gene expression.Top line shows schematic organization of regulatory regions in relation to a gene. These can vary in copy number, number of elements, number of repeats and their arrangement relative to the gene. Bottom of figure shows the nature of protein complexes in a chromosomal region of a gene being expressed. Various components of the regulation process, including Transcription Activating Factors (TAF), are shown generically. Reprinted from (Wray et al. 2003) with permission.

Figure 4-7. Basic cis-regulation of gene expression.Top line shows schematic organization of regulatory regions in relation to a gene. These can vary in copy number, number of elements, number of repeats and their arrangement relative to the gene. Bottom of figure shows the nature of protein complexes in a chromosomal region of a gene being expressed. Various components of the regulation process, including Transcription Activating Factors (TAF), are shown generically. Reprinted from (Wray et al. 2003) with permission.

transcription factors (TFs). These DNA-binding regulatory factors are encoded by genes elsewhere in the genome.

REs are typically very short (e.g., 5 to 10 base pairs) sequences, often assembled into regulatory modules or cassettes. This is shown schematically in Figure 4-7. A module typically contains binding sites for four to eight TFs, but there is no fixed number or arrangement or even location relative to the gene. A cluster of such elements is sometimes jointly called a locus control region (LCR), and can be quite distant from the gene itself. The TFs binding in such a region are often from different gene families. When in place, the configuration of TFs attract and enable the polymerases and other basal RNA transcription machinery.

Many regulatory proteins typically assemble in the regulatory region of a gene when it is to be expressed and interact in a variety of ways, including direct proteinprotein as well as protein-DNA binding. Products of the Sox family of genes produce bends or loops in DNA near a gene, to enable other regulatory proteins to bind there. The number, location, or specific sequence details (e.g., binding affinities) of the REs can quantitatively affect expression levels. There are other sequence elements, for example, insulators that prevent multiple neighboring genes from being expressed at the same time.

Table 4-4 provides some examples of TF recognition sequences. This sequence information is not unambiguous, in that related TFs may recognize similar binding motifs, so there can be crossreaction; for example, many Hox genes (that is, their coded proteins) recognize motifs like ATTAAATTA. POU domains recognize sequences like ATTTGCAT. Some leucine zipper TFs bind CCAAT.

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