Chapter 14: Gene Regulation

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Gene Regulation in Bacteria and Eukaryotes: An Overview

• Bacterial cells grow rapidly and have a relatively short lifespan.
  • Transcriptional-level control is the most common way for the prokaryotic cell to regulate gene expression.
• Eukaryotic cells usually have a relatively long lifespan during which they must maintain homeostasis in response to many different stimuli.
  • Regulatory control at all levels of gene expression allows cells to rapidly and reversibly respond to changing physiological conditions.
• A mutation in only one gene and that each gene affected only one enzyme.
• Much gene regulation in multicellular organisms is focused on the differential expression of genes in the cells in various tissues.
• A genetic mutation in pigs makes them develop more muscle tissue.
  • The mutation is in a gene, designated insulin-like growth factor 2 (IGF2), which codes for a protein produced by both muscle and liver tissues.
  • The biologists found that a base-substitution mutation in the IGF2 gene makes the gene three times more active in pig muscles, resulting in leaner meat.

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Gene Regulation in Bacteria

• An operon is a gene complex consisting of a group of structural genes with related functions plus the closely linked DNA sequences responsible for controlling them.
• Each operon has a single promoter region upstream from the protein-coding regions; the promoter is where RNA polymerase first binds to DNA before transcription begins.
• The operator serves as the regulatory switch for transcriptional-level control of the operon.
  • The binding of a repressor protein to the operator sequence prevents transcription; although RNA polymerase binds to the promoter, it is blocked from transcribing the structural genes.
  • When the repressor is not bound to the operator, transcription proceeds.
• An inducible operon, such as the lac operon, is normally turned off.
  • The repressor protein is synthesized in an active form that binds to the operator.
  • If lactose is present, it is converted to allolactose, the inducer, which binds to the repressor protein.
  • The altered repressor cannot bind to the operator, and the operon is turned on.
• A repressible operon, such as the trp operon, is normally turned on.
  • The repressor protein is synthesized in an inactive form that cannot bind to the operator.
  • A metabolite (usually the end product of a metabolic pathway) acts as a corepressor.
  • When corepressor levels are high, a corepressor molecule binds to the repressor, which can now bind to the operator and turn off transcription of the operon.
• Constitutive genes are neither inducible nor repressible; they are active at all times.
  • The activity of constitutive genes is controlled by how efficiently RNA polymerase binds to their promoter regions.
• Repressible and inducible operons are under negative control.
  • When the repressor protein binds to the operator, transcription of the operon is turned off.
• Some inducible operons are also under positive control, in which an activator protein binds to the DNa and stimulates transcription of the gene.
  • Catabolite activator protein (CAP) activates the lac operon; Cap binds to the promoter region, stimulating transcription by binding RNA polymerase tightly.
  • To bind, Cap requires cyclic AMP (cAMP), which increases in the cell as glucose decreases.
• Some post transcriptional controls operate in bacteria.
  • A translational control is a posttranscriptional control that regulates the rate of translation of a particular mRNA.
  • Posttranslational controls include feedback inhibition of key enzymes in some metabolic pathways.

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Gene Regulation in Eukaryotic Cells

• Eukaryotic genes are not normally organized into operons.
  • Regulation of eukaryotic genes occurs at the levels of transcription, mRNA processing, translation, and modifications of the protein product.
• Transcription of a gene requires a transcription initiation site, where transcription begins, plus a promoter to which RNA polymerase binds.
  • In almost all multicellular eukaryotes, the promoter contains an element called the TATA box that has a regulatory function and facilitates expression of the gene.
• Some eukaryotic genes have enhancers and silencers located thousands of bases away from the promoter.
  • These regulatory elements increase or decrease the rate of transcription.
• Eukaryotic genes are controlled by DNA-binding proteins called transcription factors.
  • Many are transcriptional activators; others are transcriptional repressors.
• Each transcription factor has a DNA-binding domain.
  • Some transcription factors have a helix-turn-helix arrangement and insert one of the helices into the DNA.
  • Other transcription factors have loops of amino acids held together by zinc ions; each loop includes an a-helix that fits into the DNA
  • Some transcription factors are leucine zipper proteins that associate as dimers that insert into the DNA
• Densely packed regions of chromosomes, called heterochromatin, contain inactive genes.
  • Active genes are associated with a loosely packed chromatin structure called euchromatin.
  • Methyl groups, acetyl groups, sugars, and proteins may chemically attach to the histone tail, a string of amino acids that extends from the DNA-wrapped nucleosome, and may expose or hide genes, turning them on or off.
• DNA methylation perpetuates gene inactivation.
  • Epigenetic inheritance is an important mechanism of gene regulation that involves changes in how a gene is expressed.
  • Because DNA methylation patterns tend to be repeated in successive cell generations, they provide a mechanism for epigenetic inheritance.
• Some genes whose products are required in large amounts exist as multiple copies in the chromosome.
  • In the process of gene amplification, some cells selectively amplify genes by DNA replication.
• As a result of alternative splicing, a single gene produces different forms of a protein in different tissues depending on how the pre-mRNA is spliced.
  • Typically, such a gene contains a segment that can be either an intron or an exon.
  • As an intron, the sequence is removed, and as an exon, the sequence is retained.
• Certain regulatory mechanisms increase the stability of mRNA, allowing more protein molecules to be synthesized before the mRNA is degraded.
  • Sometimes mRNA stability is under hormonal control.
• Posttranslational control of eukaryotic genes occurs by feedback inhibition or by chemical modifications that change the protein’s structure.
  • The function of a protein is changed by kinases adding phosphate groups or by phosphatases removing phosphates.
• Posttranslational control of gene expression also involves protein degradation.
  • Proteins targeted for destruction are covalently bonded to ubiquitin, which tags it for degradation in a proteasome, a large macromolecular structure.
  • Proteases associated with proteasomes degrade the protein into short peptide fragments.

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