Introduction to Bacterial Gene Regulation Transcriptional

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Introduction to Bacterial Gene Regulation
(Transcriptional)

• An overview of intracellular space
• The bacterial operon
• Promoters
• Sigma factors
• Repressors
• Activators
• Effector molecules

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Promoter

• Binding site for RNA Polymerase (RNAP)
• Site of initiation of mRNA
• Often constitutive in bacteria default is
  on
• Note this use of constitutive means capable of
  being active without activation does not mean
  unregulated
• Sigma factor determines specificity the DNA
  sequence that RNAP binds
• Multiple sigma factors different classes of
  promoters

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Repressors

• turn off gene expression
• Typically work by simply blocking access to the
  promoter by RNAP
• An effector molecule can either lead to
  repression or de-repression, depending on whether
  the protein binds to DNA with or without the
  effector molecule

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Activators

• Increase the expression from a promoter usually
  for promoters that are intrinsically weak
• Typically protein-protein interactions increases
  the affinity of RNAP for promoter
• Effector can either cause activation or
  de-activation

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Specificity of DNA binding proteins

• Refers to the proteins ability to bind to some
  sequences better than others
• Often referred to by a consensus sequence a
  DNA sequence that represents a typical binding
  site
• TATAAT for -10 region of promoter
• Better descriptions by allowing different scores
  for different bases at each position

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Weight Matrix Model
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Weight Matrix Model
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.A C T A T
A A T G T
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Weight Matrix Model
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.A C T A T
A A T G T
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N(b,i) F(b,i) S(b,i) logF(b,i)/P(b)
I(i) ?F(b,i)S(b,i) b
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A 0 3 79 40 66 48 65 11 65 0 C 94 75
4 3 1 2 5 2 3 3 G 1 0
3 4 1 0 5 3 28 88 T 2 19 11 50
29 47 22 81 1 6
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Likelihood Ratio Statistics Primer
Given two probability distributions Pi and QI ?
Pi ?Qi 1
And some data, Di, which is number of times each
type i is observed in N total observations
The Likelihood Ratio of the data being from
distribution Qi versus Pi is LR ? (Qi/Pi)Di
And the log-Likelihood Ratio is LLR ? Di ln
(Qi/Pi)
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LLR ? Di ln (Qi/Pi) Maximum likelihood
distribution is Qi Di/N So max LLR N ? Qi ln
(Qi/Pi)
? Qi ln (Qi/Pi) 0 Information Content
Relative Entropy Kullbach-Liebler
Distance Related to G-statistic and ?2