Control of Gene Expression

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Chapter 8

• Control of Gene Expression

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Gene Expression

• Determine which genes are on or off in a cell
• Neuron and lymphocyte have the same DNA but only
  use a subset of those genes originally thought
  that cells lost the DNA that they dont use

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Differentiation

• Process by which cells can become a particular
  type like neuron or lymphocyte
• All cells from an organism has the same DNA and
  can potentially make a new organism

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Sets of Proteins

• Some proteins are common to all cells called
  housekeeping proteins
• Required for proteins of chromosomes, RNA
  polymerase, DNA repair enzymes and ribosomal
  proteins
• Some proteins are special to certain cell types
• Hemoglobin is found in RBCs but no other cell

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External Signals

• Signals from outside the cell can cause the
  protein expression inside the cell to change
• May increase the protein level or lower the level
  of the protein
• Remove the signal and the cell will go back to
  normal levels
• Different cells respond differently to the signals

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Gene Expression Regulation

• Control is at many steps
• Control when and how often a given gene is
  transcribed
• Most important step of control
• Control how primary transcript is spliced and
  processed
• Control which mRNA are translated by ribosomes
• Activated or inactivate protein after made

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Transcriptional Switches

• Gene regulatory proteins switch genes off and
  on
• Protein binds to regulatory DNA sequences
• Promoter for RNA polymerase and initiation sites
  where transcription begins also bind these
  proteins
• Genes expressed or not depends on
• Type of cell
• Surroundings
• Age of cell
• Extracellular signals

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Switches

• Bacteria have simple switches
• Eukaryotes have very long sequences
  microprocessor
• Respond to a variety of signals integrates into
  the instructions

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Interactions

• Regulatory sequence must recognize the regulatory
  DNA sequence which is specific
• Use H-bonds, ionic bonds and hydrophobic
  interactions to hold together
• The folding pattern of protein allows it to fit
  in the groove of DNA

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DNA Binding Motifs

• Can recognize many different DNA sequences by a
  limited number of proteins
• Homeodomain helix turn helix structure
• Zinc finger - ? helix and ? sheet held together
  with zinc
• Leucine zipper 2 ? helices in 2 proteins
• Clothespin on a clothes line

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Repressors and Activators

• E coli DNA encodes about 4300 proteins but not
  all at the same time
• Bacteria regulate gene expression based on
  available food sources
• 5 genes encode the proteins to make tryptophan
  from a single promoter, clustered together in an
  operon
• Off when trp is available and on when no trp

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Tryptophan Operon
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Operon Function

• Promoter has short DNA sequence recognized by
  gene regulatory protein operator
• Tryptophan repressor can bind to promoter and
  block access to RNA polymerase
• Prevent transcription
• Repressor can only bind to DNA only if several
  molecules of trp are bound to it no need for
  synthesis if it is available in medium
• As levels of trp falls, the trp leaves the
  repressor and then the RNA polymerase can bind to
  the promoter and initiate the transcription of
  necessary proteins

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Trp Operon
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Repressor Regulation

• Operon is regulated by the end product
• As trp levels go up, trp can bind to repressor
  and cause a shape change that opens the area that
  binds to the DNA
• Repressor is always present unregulated gene
  expression is called constitutive expression
  (always on)

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Activator Switches

• Activators turn on gene expression
• Normally, bacterial promoters are marginally
  functional in binding promoter and recruiting RNA
  polymerase need the activator to make the
  transcript
• Activator CAP must bind cAMP before binding DNA
• See increase in cAMP when glucose levels fall and
  need to make the enzymes/proteins necessary for
  using other sugar sources

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Activators
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Lac Operon

• Allows bacteria to use lactose as a carbon source
• Controlled by lac repressor to keep off and CAP
  activator to turn on
• Glucose levels fall and turns on CAP
• If glucose level is high, dont need so the lac
  repressor comes in and shuts off the operon, also
  occurs when no lactose present
• Must meet to criteria
• Lactose must be present
• Glucose must be absent

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Lac Operon
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Eukaryotic Gene Expression

• Much more complicated, responds to many signals
• Regulation has 4 parts
• 3 RNA polymerases with different function vs 1
  for bacterial
• Bacterial polymerase needs no help, eukaryotic
  RNA polymerase needs general transcription
  factors that must be on the promoter before
  polymerase
• Activators and repressors are on the DNA and may
  be 1000s of nucleotides from the promoter area
• Must deal with nucleosomal DNA

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Eucaryotic RNA Polymerases