Controls over Genes

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Chapter 15

• Controls over Genes

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Overview. Gene Control is

• Mechanisms that govern when/how fast genes will
  be transcribed and translated
• And whether genes will be
• silenced or switched on
• As a result
• Rates of transcription and
• translation will change
• Rates also change due to nutrient uptake
• Cell differentiation results from
• certain genes being expressed
• Right Cell differentiation in neurons and
  epithelial cells

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Overview (cont)

• Mutagenic agents can also cause change in gene
  regulationwhat kind causes skin cancer?
  Non-ionizing
• 7 gene products act as DNA repair mechanism for
  repairing skin lesions
• One mutation can create Thymine-dimers that
  accumulate which can trigger cancer cell growth
• Basal Cell Carcinoma (most common, raised lump,
  uncolored, red-brown or black) Far Right
• Squamous Cell Carcinoma (2nd most common, pink,
  firm to touch) Middle
• Malignant Melanoma (Fastest spreading, dark,
  encrusted itchy lumps) Far Left

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15.1 Types of control mechanisms

• Control Agents
• Regulatory proteins
• Intervene anytime around or during transcription
• or translation, also includes hormones
• Can be negative or positive
• Enhancers and Promoters
• Promoters are sequences that signal
• the start of the gene (above right)
• Enhancers are binding sites
• for activator proteins (below right)

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5.1 (cont.)

• Chemically altering DNA also way of exerting
  control
• Methylation (CH3) often inactivates genes (bottom
  right, methylation of Cytosine)
• Acetylation (COOH) can organize DNA (happens with
  histones)
• (seen below) Acetylation of various histones
• creates changes in DNA that can be
• passed down to daughter cell chromosomes

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5.2 Bacterial Control of Transcription

• E. coli lives in gut of mammals, feeding off of
  sugars
• Infants feed off of milk, which does not contain
  glucose E. coli needs, but does have lactose
  (E.coli shown below)
• E. coli uses lactose operon to survive
• Operator. Binding site for repressor protein that
  can prevent gene transcription
• Operon. Promoter and set of
• operators control more than
• one bacterial gene

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15.2 (cont.)

• In absence of lactose,
• the repressor molecule binds
• to a set of operators
• Binding causes the
• promoter to loop out,
• making the promoter
• inaccessible to RNA
• polymerase (stopping
• transcription)
• When lactose is present,
• sugar binds to repressor,
• altering its shape, re-starting
• RNA transcription

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15.2 (cont.)

• If there is no glucose, an activator protein is
  needed to exert a positive control on the
  lactose operon to make the promoter more
  inviting for RNA polymerase
• CAP is the
• protein, which must
• bind to cAMP
• (a chemical messenger)
• that helps
• transcription occur

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15.2 (cont.)

• If glucose is plentiful and lactose is not needed
  to be transcribed, an enzyme needed to synthesize
  cAMP is inhibited
• The control over this enzyme fluctuated depending
  on the level of glucose in the blood
• Humans are born with a gene for lactase
• If this lactose-digesting enzyme is
• missing, people are lactose intolerant
• Right the action of
• lactase forming
• galactose and glucose
• Far Right Lactase shown
• in microvilli of small
• intestine

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15.3 Gene Control in Eukaryotic cells

• Cell differentiation happens on multiple levels,
  beginning with totipotent stem cells

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15.3 (cont.)

• Gene control before Transcription
• 1. Gene amplification (multiple DNA replications,
  see below)
• 2. DNA rearrangements (different versions of
  antibodies from B-cell lymphocytes)
• 3. Chemical modification
• (methylation of histones,
• more in 15.3)

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15.3 B Lymphocyte cells create different versions
of antibodies
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15.3 (cont.)

• Gene control during transcription
• Introns can be cut out of pre-mRNA (alternative
  splicing)
• Ex) Troponin-1 (contractile protein) due to
  intron splicing, slightly different versions of
  these proteins are created
• may account for different type of muscle in the
  body

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15.3 (cont.)

• Controls over rate of translation
• 1. Determine how fast, when, and how many
  transcripts are translated
• The 3 poly-A tail determines how fast the mRNA
  is digested

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15.3

• Controls following
• translation
• 1. Proteins undergo modification
• in the endomembrane system
• (enzymes attach oligosaccharides to
• new polypeptide chains after translation)
• 2. Mechanisms control these
• enzymes ex) allosteric control of
• Tryptophan (see right)

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15.4 Types of control mechanisms

• Eukaryotes rarely use more than 5-10 of their
  genes at any given time. That accounts for a lot
  of control mechanisms taking place
• Homeotic genes. Class of master genes that
  interact w/ control elements to form tissue and
  organs
• homeobox binds to promoter and enhancers
• Scientists know of more than 100 homeo
• domain proteins that control transcription
• Right homeotic genes that code for various
  traits on
• the drosphila fruit fly

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15.5 Examples of signaling mechanisms

• Growth hormone (GH)- released from pituitary
  gland
• secretes insulin-like growth factor (IGF) from
  liver IGF, GH and thyroid hormone stimulate
  skeletal growth.
• stimulates protein synthesis and inhibits uptake
  of glucose in muscle
• Releases fatty acids in adipose
• tissue to be used as energy
• source in muscle tissue
• GH secretion occurs
• sporadically a single test of GH
• level is usually not performed

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15.5 (cont.)

• Hormones are major group of signaling molecules
• Ecdysone (hormone key in insect larval
  development)
• Polytene chromosome. Multiple copies of
• DNA in a parallel array useful for stock-piling
• DNA to make copius amounts of proteins for
• saliva to digest food in developing larvae
• Prolactin (hormone activated milk
• production in female mammals (right)

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15.5 (cont.)

• Sunlight initiates light-dependent
• reaction of photosynthesis
• Phytochrome. (blue green pigment) helps plants
  adapt to changes in sunlight
• Maintains active and inactive forms (see above)
• At sunset or night, far-red wavelengths dominate
  (inactive)
• At sunrise, red wavelengths are in abundance
  (activate pigment to specify enzymes to help
  seeds germinate, stems and leaves to grow)