Lecture 18

• Eukaryote


  Cells with a nucleus
• Bacteria often respond to environmental change by regulating transcription
• Natural selection has favored bacteria that produce only the products needed by that cell
• A cell can regulate the production of enzymes by feedback inhibition or by gene regulation
• Gene expression in bacteria


  Controlled by the operon model
• Operon


  A cluster of functionally related genes under coordinated control by a single on-off "switch"
• Operator


  A regulatory "switch" segment of DNA usually positioned within the promoter
• Repressible operon


  Usually on, binding of a repressor to the operator shuts off transcription
• Inducible operon


  Usually off, a molecule called an inducer inactivates the repressor and turns on transcription
• Tryptophan operon


  1. Tryptophan absent, repressor inactive, operon on

  2. Tryptophan present, repressor active, operon off
• Lac operon


  1. Lactose absent, repressor active, operon off

  2. Lactose present, repressor inactive, operon on
• Inducible enzymes


  Function in catabolic pathways, synthesis induced by a chemical signal
• Repressible enzymes


  Function in anabolic pathways, synthesis repressed by high levels of the end product
• Regulation of the trp and lac operons involves negative control of genes because operons are switched off by the active form of the repressor
• Eukaryotic gene expression can be regulated at any stage
• All organisms must regulate which genes are expressed at any given time
• In multicellular organisms gene expression is essential for cell specialization
• Almost all the cells in an organism are genetically identical
• Differential gene expression


  The expression of different genes by cells with the same genome
• Errors in gene expression can lead to diseases including cancer
• Levels of gene expression control in eukaryotes

  • Chromatin modification
  • Transcription
  • RNA processing
  • mRNA degradation
  • Translation
  • Protein processing and degradation
• Chromatin


  A complex of DNA and protein found in the nucleus of eukaryotic cells
• Histones


  Proteins responsible for the first level of DNA packing in chromatin
• Genes within highly packed heterochromatin are usually not expressed
• Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression
• DNA packaging


  1. DNA double helix (2 nm in diameter)

  2. Nucleosome (10 nm in diameter)

  3. Nucleosomes strung together like beads on a string by linker DNA (10-nm fiber)

  4. 30-nm fiber

  5. Chromatid (700 nm)

  6. Metaphase chromosome (1,400 nm)
• Euchromatin


  Loosely packed chromatin that makes genes accessible for transcription
• Heterochromatin


  Highly condensed chromatin that makes it difficult for the cell to express genetic information
• Housekeeping genes


  Genes that are always necessary and expressed in euchromatin
• Silenced genes


  Genes that are not expressed and located in heterochromatin
• Histone acetylation


  Acetyl groups attached to positively charged lysines in histone tails, promoting loose chromatin structure
• Histone methylation


  Addition of methyl groups that can condense chromatin
• Histone phosphorylation


  Addition of phosphate groups that can loosen chromatin
• Histone code


  Specific combinations of histone modifications that help determine chromatin configuration and influence transcription
• DNA methylation


  Addition of methyl groups to cytosines associated with reduced transcription
• Genomic imprinting


  Methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of development
• Epigenetic inheritance


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


  Segments of noncoding DNA that help regulate transcription by binding certain proteins
• Enhancer


  A group of distal control elements that can activate transcription
• Activator


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