Chapter 19 Control of Eukaryotic Genome

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Chapter 19Control of Eukaryotic Genome

• Eukaryotic genomes are highly ordered structures.
• Gene Expression is controlled by many different
  factors that come together in the nucleus.
• 3) There is also post-transcription and post-
  translation control of gene products

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• According to Human Genome Project info. our
  genome contains estimated 20,000 to 25,000 genes.
  (your book says 35,000)
• Only about 3 of our genome actually codes for
  proteins.
• Only 5 years ago, we estimated 80,000 genes

Next step is proteomics Protein products and
what they do
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Chromatin Structure

• Each chromosome has a DNA double helix molecule
  that averages about 200,000,000 nucleotide bases
  long. 6cm if laid out straight.
• (Average cell diameter is 10 µm)
• We have 46 of these chromosomes.
• All this DNA needs to be packed in an orderly
  fashion.

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Nucleosomes

• 1st level of DNA packing.
• DNA is wrapped around 8 histone proteins and 1 H1
  protein sits outside of nucleosome.

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3 nucleosomes shown here
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30 nm chromatin fiber loop domains

• With help of histone protein on outside, the
  nucleosomes coil to form a fiber that is 30nm in
  diameter.

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30 nm fiber packing
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Loop Domains

• The 30 nm fibers are arranged in loops.
• Red line represents scaffold for hold loops
  together.

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DNA packing overview
Naked DNA Nucleosomes 30 nm fiber Loop
domains Euchromatin or heterochromatin
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Chromatin arrangement

• There are two types of chromatin found in a
  nucleus at any given time
• 1) Heterochromatin
• 2) Euchromatin

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• Heterochromatin is highly condensed chromatin,
  even in interphase, or when cell is not dividing.
• Euchromatin is more diffuse, more loosely packed.
• DNA in nucleus

Euchromatin
heterochromatin
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Genome Organization

• A lot of our DNA is made of repetitive sequences
  that does not necessarily code for any product!
• These are called Repetitive DNA sequences.
• 1) Tandomly repetitive DNA
• 2) Interspersed repetitive DNA.

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Tandemly Repetitive DNA

• These are short sequences in tandem (one right
  after another)
• Eg) CGAAT/CGAATCGAATCGAAT
• They can be repeated from 10 times to several
  hundred thousand times!
• Find most of these sequences at centromere
  telomere regions

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Tandemly repetitive DNA disorders.

• Fragile X
• Huntingtons Disease

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Interspersed Repetitive DNA

• These repetitive segments are not next to each
  other, but scattered in genome.
• Function not well understood.
• But thought to arise from transposons (mobile
  genetic elements)
• About 25-40 of mammalian genome.

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Transposons mobile genetic elements

• These are stretches of DNA that can move from one
  location to another within the genome.
• This means genes get shuffled sometimes.
• This is critical to making our antibodies.

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Transposons can be harmful. Are responsible for
moving bacterial plasmid genes to genome and
visa versa
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The reddish streaks on these Indian corn grains
are caused by transposons.
The movement of transposons on chromosomes may
result in colored, non-colored and striped
grains that do not fit traditional Mendelian
ratios
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Multi-Gene Families

• A group of genes that are identical or very
  similar.
• Some genes in a family may be grouped together
  (or right next to each other), or can also be
  scattered throughout .
• You can have several identical genes in your
  genome!
• More genes more possible gene products

Family tree of similar genes
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Gene families

• The number of genes in a gene family can change!
• The cell can amplify a genes number if it needs
  many of its products.
• You can also lose or rearrange genes.
• The rearrangement can sometimes cause
  problemshow?

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Controlling Gene Expression

• 1) Accessibility to gene for transcription.
• Enhance/inhibit the gene before/during
  transcription.
• Factors that regulate the mRNA
• Factors that regulate the new peptide (gene
  product)

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1) Factors in DNA Accessibility

• DNA, as you remember, is wrapped around
  nucleosomes, then that is wrapped into 30nm
  fibers, then that is arranged in packed loops
• How can anything reach DNA like this?

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Histone Acetylation

• This is one mechanism to loosen nucleosomes up.
• When an acetly group
• (-COCH3) is attached to a histone protein, it
  causes a conformational change in the protein
  (protein changes shape).
• This shape change loosens its hold on DNA, so
  transcription factors can come in an start
  transcription.

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Methylation

• When a methyl group (CH3) is attached to some
  bases of DNA, it has been found to shut the gene
  off
• Remove methyl group re-activate the gene.

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Acetylation of histone usually turns a gene on.
Methylation of histone or DNA usually turns a
gene off.
We do not talk about phosphorylation
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2) Transcription factors

• Transcription factors is a generic term for
  proteins which help in controlling the expression
  of a gene at special regulatory regions on the
  DNA.

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• Transcription factors can enhance or repress
  genes based on where they bind on the DNA
  molecule.
• At every gene, there is a promoter region (with
  the TATA box), enhancer regions and silencer
  regions.
• T.F.s work together to accomplish a task. Ie)
  some TFs have binding sites for DNA and binding
  sites for other TFs.

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(No Transcript)
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3) Post transcriptional Control

• After a gene has been transcribed into a RNA
  molecule, it can be spliced into alternative
  forms.
• Regulatory proteins specific to the cell will
  recognize areas to splice RNA.
• Can get more than one kind of polypeptide from
  one gene!

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Different protein products from same mRNA
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Alternative RNA splicing and immune system
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mRNA degradation

• The life span of mRNA inside the cell is limited.
• Enzymes break down the 5G-cap and 3 poly A tail
  then let other enzymes break down rest of RNA
  molecule.

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Control of translation

• Regulatory proteins will bind at the 5 end of
  mRNA.
• Ribosome recognizes 5 end to begin translation.
• So this protein stops translation from happening.

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inhibitor
3
mRNA
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4)Post translational control

• Ubiquitin is a small protein that binds proteins
  that need to be broken down.
• This serves as a signal to other enzymes in the
  cell to target that protein and break it down.

ubiquitin
Protein pieces
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Genes Cancer

• Cancer is caused by cells that have lost the
  ability to control replication.
• Our cells have many genes that code for
  cell-cycle machinery.
• The genes that code for proteins involved in cell
  growth and division are called proto-oncogenes.
• If these genes are mutated, they can convert to
  oncogenes.

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Proto-Oncogenes Oncogenes
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Tumor Suppressor Genes
Genes that code for proteins that are involved
in inhibiting cell growth are called
tumor-suppressor genes.
Example p53
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Cancer

• At least 6 different changes need to occur to
  transform a cell to a fully cancerous cell.
• Here are only a few
• At least one active oncogene
• Mutation or loss of a tumor suppressor gene.
  (these mutations have to occur on both alleles!)
• Gene for telomerase is activated, this elongates
  telomere regions, gives cell more future
  replications than what should occur naturally.

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• Viruses seem to play a role in cancer. (about
  15 of human cancer cases)
• Eg) Human Papilloma Virus (HPV)
• Sometimes our DNA repair genes are mutated, we
  can accumulate more mutations and lead to cancer.

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Warts
Human Papilloma Virus 60 different typescause
all kinds of warts Genital, palmer, plantar etc.