32.1 Eukaryotic DNA Is Organized into Chromatin

Eukaryotic DNA is tightly bound to basic proteins called histones; the combination is called chromatin. DNA wraps twice around an octamer of core histones to form a nucleosome. The four core histones are homologous and fold into similar structures. Each core histone has an amino-terminal tail rich in lysine and arginine residues. Nucleosomes are the first stage of compaction of eukaryotic DNA. Chromatin blocks access to many potential DNA-binding sites. Changes in chromatin structure play a major role in regulating gene expression.

32.2 Transcription Factors Bind DNA and Regulate Transcription Initiation

Most eukaryotic genes are not expressed unless they are activated by the binding of specific proteins, called transcription factors, to sites on the DNA. These specific DNA-binding proteins interact directly or indirectly with RNA polymerases or their associated proteins. Eukaryotic transcription factors are modular: they consist of separate DNA-binding and activation domains. Important classes of DNA-binding proteins include the homeodomains, the basic-leucine zipper proteins, and Cys₂His₂ zinc-finger proteins. Each of these classes of proteins uses an α helix to make specific contacts with DNA. Activation domains interact with RNA polymerases or their associated factors or with other protein complexes such as mediator. Enhancers are DNA elements that can modulate gene expression from more than 1000 bp away from the start site of transcription. Enhancers are often specific for certain cell types, depending on which DNA-binding proteins are present. The introduction of genes for a specific set of four transcription factors into fibroblasts can cause these cells to dedifferentiate into induced pluripotent stem cells.

32.3 The Control of Gene Expression Can Require Chromatin Remodeling

Chromatin structure is crucial to the control of gene expression; it is more open near the transcription start sites of actively transcribed genes. Steroids such as estrogens bind to eukaryotic transcription factors called nuclear hormone receptors. These proteins are capable of binding DNA whether or not ligands are bound. The binding of ligands induces a conformational change that allows the recruitment of additional proteins called coactivators. Among the most important functions of coactivators is to catalyze the addition of acetyl groups to lysine residues in the tails of histone proteins. Histone acetylation decreases the affinity of the histones for DNA, making additional genes accessible for transcription. In addition, acetylated histones are targets for proteins containing specific binding units called bromodomains. Bromodomains are components of two classes of large complexes: (1) chromatin-remodeling engines and (2) factors associated with RNA polymerase II. These complexes open up sites on chromatin and initiate transcription.

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32.4 Eukaryotic Gene Expression Can Be Controlled at Posttranscriptional Levels

Genes encoding proteins that transport and store iron are regulated at the translational level. Iron-response elements, structures that are present in certain mRNAs, are bound by an IRE-binding protein when this protein is not binding iron. Whether the expression of a gene is stimulated or inhibited in response to changes in the iron status of a cell depends on the location of the IRE within the mRNA. The IRE-binding protein is a cytoplasmic aconitase that loses its iron–sulfur center under low-iron conditions. MicroRNAs are specialized RNA molecules encoded as parts of larger RNA precursors. They bind to proteins of the Argonaute family; the bound miRNAs function as guides that help bind specific mRNA molecules that are then cleaved.