James 4:7

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• James 47
• 7 Submit yourselves therefore to God. Resist the
  devil, and he will flee from you.

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Transcription Regulation

• Timothy G. Standish, Ph. D.

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Eukaryotic RNA Polymerase II Promoters

• Eukaryotic promoters comprise several sequence
  elements spread over about 200 bp upstream from
  the transcription start site
• 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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Eukaryotic Promoters
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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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Heat Shock Response Elements

• Sudden changes in the temperature of cells cause
  stress in response to which heat shock genes are
  expressed
• At least some heat shock genes are thought to be
  chaperones that help proteins fold correctly
• Heat shock genes have Heat Shock Elements (HSEs)
  in their control regions
• Heat Shock Transcription Factors (HSTFs) bind the
  HSEs up regulating expression of heat shock gene
  products

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The Heat Shock Response
HSTF
Kinase
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The Heat Shock Response
Activation of kinase
HSTF
Kinase
Phosphorylation of HSTF
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The Heat Shock Response
Activation of HSTF
Kinase
HSTF
Transcription initiation of all heat shock genes
with HSEs
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Methallothionein Regulation

• Heat shock protein regulation illustrates how a
  group of genes can be regulated by a single
  transcription factor
• Other genes are regulated by a group of
  transcription factors
• This allows them to either respond to multiple
  separate situations, or respond only to a
  specific combination of situations
• Metallothionein is an example of a gene that can
  be turned on by multiple transcription factors

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Metallothionein Regulation
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Regulation By TFs

• A single transcription factor (or group of
  transcription factors) may regulate expression of
  a group of genes (i.e. heat shock proteins)
• A single gene may be regulated by a number of
  independent transcription factors (i.e.
  metallothionine)
• Eukaryotic regulation does not seem to involve
  repression
• To achieve high levels of expression, several
  different transcription factors binding to
  different response elements may be necessary

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How Do TFs Recognize Response Elements?

• Some mechanism must exist for protein
  transcription factors to recognize the specific
  sequences of bases found in response elements
• There is no known specific relationship between a
  given amino acid and a base that would allow
  direct recognition
• Groups on bases that are not involved with base
  pairing have the potential to be recognized by
  proteins
• Some specific sequences are known to influence
  the gross structure of DNA

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DNA Binding Domains

• Transcription factors exhibit a number of
  different motifs found in the area known to bind
  DNA
• Zinc finger -First found in TFIIIA
• Helix-turn-helix - First described from phage
  receptors
• Amphipathic Helix-loop-helix - Identified in some
  development regulators
• Leucine zipper - Held together by interactions
  between leucine amino acids

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Zinc Fingers

• Are found in steroid receptors and are common in
  other transcription factors
• Interaction between cysteine and histidine amino
  acids and the divalent zinc ion results in the
  formation of loops called fingers
• One side of each loop forms an a-helix which can
  lie in the major grove of DNA
• Interaction between the amino acids in the zinc
  finger and bases in the DNA allow for sequence
  recognition

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Zinc Fingers
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Zinc Fingers
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