Hebrews 1

1

• Hebrews 1
• 1 God, who at sundry times and in divers manners
  spake in time past unto the fathers by the
  prophets,
• 2 Hath in these last days spoken unto us by his
  Son, whom he hath appointed heir of all things,
  by whom also he made the worlds

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Gene Regulation - Eukaryotes

• Timothy G. Standish, Ph. D.

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Control Of Expression In Eukaryotes

• Some of the general methods used to control
  expression in prokaryotes are used in eukaryotes,
  but nothing resembling operons is known
• Eukaryotic genes are controlled individually and
  each gene has specific control sequences
  preceding the transcription start site
• In addition to controlling transcription, there
  are additional ways in which expression can be
  controlled in eukaryotes

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Eukaryotes Have Large Complex Geneomes

• The human genome is about 3 x 109 base pairs or
  1 m of DNA
• Because humans are diploid, each nucleus contains
  6 3 x 109 base pairs or 2 m of DNA
• That is a lot to pack into a little nucleus!

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Only a Subset of Genes is Expressed at any Given
Time

• It takes lots of energy to express genes
• Thus it would be wasteful to express all genes
  all the time
• By differential expression of genes, cells can
  respond to changes in the environment
• Differential expression, allows cells to
  specialize in multicelled organisms.
• Differential expression also allows organisms to
  develop over time.

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Control of Gene Expression
Packaging
Transportation
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Logical Expression Control Points

• DNA packaging
• Transcription
• RNA processing
• mRNA Export
• mRNA masking/unmasking and/or modification
• mRNA degradation
• Translation
• Protein modification
• Protein transport
• Protein degradation

The logical place to control expression is before
the gene is transcribed
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Eukaryotic DNA Must be Packaged

• Eukaryotic DNA exhibits many levels of packaging
• The fundamental unit is the nucleosome, DNA wound
  around histone proteins
• Nucleosomes arrange themselves together to form
  higher and higher levels of packaging.

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Packaging DNA
Metaphase Chromosome
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Highly Packaged DNA Cannot be Expressed

• The most highly packaged form of DNA is
  heterochromatin
• Heterochromatin cannot be transcribed, therefore
  expression of genes is prevented
• Chromosome puffs on some insect chomosomes
  illustrate where active gene expression is going
  on

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Eukaryotic RNA Polymerase II

• RNA polymerase is a very fancy enzyme that does
  many tasks in conjunction with other proteins
• RNA polymerase II is a protein complex of over
  500 kD with more than 10 subunits

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Eukaryotic RNA Polymerase II Promoters

• Several sequence elements spread over about 200
  bp upstream from the transcription start site
  make up RNA Pol II promoters
• Enhancers, in addition to promoters, influence
  the expression of genes
• Eukaryotic expression control involves many more
  factors than control in prokaryotes
• This allows much finer control of gene expression

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Initiation
T. F.
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Eukaryotic RNA Polymerase II Promoters

• Eukaryotic promoters are made up of a number of
  sequence elements spread over about 200 bp
  upstream from the transcription start site
• In addition to promoters, enhancers also
  influence the expression of genes
• Control of gene expression in eukaryotes involves
  many more factors than control in prokaryotes
• This allows much finer control of gene expression

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A Simple Eukaryotic Gene
Transcription Start Site
3 Untranslated Region
5 Untranslated Region
Introns
3
5
Int. 2
Int. 1
Exon 2
Exon 3
Exon 1
Terminator Sequence
Promoter/ Control Region
Exons
RNA Transcript
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Eukaryotic Promoters
(Template strand)
-25
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Response Elements

• Response elements are short sequences found
  either within about 200 bp of the transcription
  start site, or as part of enhancers
• Different genes have different response elements
• Binding of transcription factors to response
  elements determines which genes will be expressed
  in any cell type under any set of conditions

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InitiationTFIID Binding
TATA Box
-11
TATA Binding Protein (TBP)
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InitiationTFIID Binding
TFIID
-11
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InitiationTFIIA and B Binding
TFIID
-11
TFIIA
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InitiationTFIIF and RNA Polymerase Binding
TFIID
-11
TFIIA
RNA Polymerase
TFIIF
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InitiationTFIIE Binding
TFIIE
TFIID
RNA Polymerase
TFIIF
-11
TFIIA
TFIIE has some helicase activity and may by
involved in unwinding DNA so that transcription
can start
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InitiationTFIIH and TFIIJ Binding
TFIIJ
TFIIE
TFIID
RNA Polymerase
TFIIF
-11
TFIIA
TFIIH has some helicase activity and may by
involved in unwinding DNA so that transcription
can start
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InitiationTFIIH and TFIIJ Binding
TFIIJ
TFIIE
TFIID
RNA Polymerase
TFIIF
-11
TFIIA
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InitiationTFIIH and TFIIJ Binding
RNA Polymerase
-11
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Enhancers
Many bases
TF
TF
TF
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(No Transcript)