18 chap

• Bacteria often respond to environmental change by regulating transcription
• Natural selection has favored bacteria that


  • Express only the genes that encode products needed by the cell
• Regulation of enzyme production

  1. Feedback inhibition

  2. Gene regulation
• Feedback inhibition


  The end product of a metabolic pathway shuts down further synthesis of the product by inhibiting enzyme activity
• Gene regulation


  Cells can adjust the production level of certain enzymes by regulating expression of the genes encoding the enzymes
• The control of enzyme production is at the level of transcription
• Operon


  The entire stretch of DNA that includes the operator, the promoter, and the genes that they control
• Operon


  • A cluster of functionally related genes can be coordinately controlled by a single "on-off switch"
  • The switch is a segment of DNA called an operator, positioned within the promoter or, sometimes, between the promoter and enzyme-coding genes
• Repressor


  A protein that prevents gene transcription by binding to the operator and blocking RNA polymerase
• Corepressor


  A molecule that cooperates with a repressor protein to switch an operon off
• Trp operon


  • E. coli can synthesize the amino acid tryptophan when it has insufficient tryptophan
  • The trp operon is turned off (repressed) if tryptophan levels are high
• Repressible operon


  An operon that is usually on; binding of a repressor to the operator shuts off transcription
• Inducible operon


  An operon that is usually off; a molecule called an inducer inactivates the repressor and turns on transcription
• Lac operon


  • An inducible operon that contains genes that code for enzymes used in the hydrolysis and metabolism of lactose
  • The lac repressor is active and switches the lac operon off
  • Allolactose, an isomer of lactose, binds the repressor protein and inactivates it to turn the lac operon on
• Inducible enzymes


  Usually function in catabolic pathways; their synthesis is induced by a chemical signal
• Repressible enzymes


  Usually function in anabolic pathways; their synthesis is repressed by high levels of the end product
• Positive gene regulation


  Some operons are also subject to positive control through a stimulatory protein, such as cyclic AMP receptor protein (CRP), an activator of transcription
• When glucose (a preferred food source of E. coli) is scarce


  • CRP is activated by binding with cyclic AMP (cAMP)
  • Activated CRP attaches to the promoter of the lac operon and increases the affinity of RNA polymerase, thus accelerating transcription
• When glucose levels increase


  CRP detaches from the lac operon, and transcription returns to a normal, low level
• Eukaryotic gene expression is regulated at many stages
• Differential gene expression


  The expression of different genes by cells with the same genome
• Abnormalities in gene expression can lead to diseases including cancer
• Chromatin structure


  • Genes within highly packed heterochromatin are usually not expressed
  • In euchromatin, gene transcription is affected by the location of nucleosomes along the promoter and the sites where DNA attaches to the protein scaffolding of the chromosome
• Histone acetylation


  Acetyl groups are attached to an amino acid in a histone tail, which appears to open up the chromatin structure and promote the initiation of transcription
• Histone methylation


  The addition of methyl groups can condense chromatin and reduce transcription
• DNA methylation


  • The addition of methyl groups to certain bases in DNA, is associated with reduced transcription
  • Can cause long-term inactivation of genes in cellular differentiation
  • In genomic imprinting, methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development
• Epigenetic inheritance


  The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence
• Control elements


  Segments of noncoding DNA that serve as binding sites for transcription factors that help regulate transcription
• General transcription factors


  Essential for the transcription of all protein-coding genes
• Specific transcription factors


  Bind to control elements that may be close to or farther away from the promoter
• Enhancers


  Distal control elements, groupings of which may be far away from a gene or even located in an intron, and are generally associated with only one gene and no other
• Activator


  A protein that binds to an enhancer and stimulates transcription of a gene
• Repressor


  A transcription factor that inhibits expression of a particular gene in several different ways
• Combinatorial control of gene activation is possible with only a dozen or so control elements
• Co-expressed eukaryotic genes are not organized in operons (with a few exceptions)
• Chromosome conformation capture techniques allow identification of regions of chromosomes that interact with each other
• Alternative RNA splicing


  Different mRNA molecules are produced from the same primary transcript, depending on which RNA segments are treated as exons and which as introns
• mRNA degradation


  Nucleotide sequences that influence the life span of mRNA in eukaryotes reside in the untranslated region (UTR) at the 3' end of the molecule
• Protein processing and degradation

  • Polypeptides undergo processing, including cleavage, and chemical modifications
  • Cells mark proteins for degradation by attaching ubiquitin to them, which is recognized by proteasomes that degrade the proteins
• A small fraction of DNA codes for proteins, and a very small fraction of the non-protein-coding DNA consists of genes for RNA such as rRNA and tRNA