The document discusses four main levels of gene expression control: transcriptional, RNA processing, translational, and post-translational. It provides details on the mechanisms of transcriptional control, including promoters, enhancers, transcription factors, silencers, and chromatin remodeling. Alternative promoters allow for different regulation of the same gene, producing different primary transcripts and mRNA processing results in the same mature mRNA.

2. Differential Gene Expression
• Transcriptional control
• RNA processing control
• Translational control
• Post-translational control
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3.  Transcriptional control
 DNA-mRNA
 mRNA processing
 and stability
 Translational control
 mRNA -Protein
 Post-Translational control
 Protein modifications
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4.  Promoter
 Transcription initiation site
 Translation initiation site
• 5’ UTR (untranslated
sequence)
 Exons (expressed)
 Introns (intervening)
 Translation termination codon
 3’UTR
• Polyadenylation addition
site
 Transcription termination site
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5. 5
Transcription initiation site
Translation initiation site
Translation termination codon
3’ Untranslated region
Promoters
Exons
Introns

6. Three main regulatory agents:
• Nuclear proteins that regulate access to DNA
• Multiple, alternative promoters
• Cells differ in number or type of transcription
factors
Let’s take a look at each…..
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7.  Nuclear proteins regulate access to
DNA
 DNA normally bound up in nucleosomes
(histone proteins)
 Chromatin remodeling proteins unwind
specific DNA sequences allowing
access to transcription initiation
complex
• Exposes enhancer and promoter regions
allowing transcription
 Detour -- now we need to learn what
enhancers & promoters are……
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8. Chromatin remodeling affects
• DNA replication & repair
• Apoptosis
• Chromosome segregation
• Pluropotency
Targeting chromatin remodeling pathways
is a growing field in targeting several
cancers (regulate mitosis)

9.  Promoter -- initiates transcription of a particular gene
(TATA box, GC islands)
 Enhancer -- short region of DNA which can be found
with proteins (TF’s) to “enhance” transcription levels in
a gene cluster
 Transcription factor -- works in conjunction with
enhancers; family of proteins; alter DNA confirmation
 Silencer -- “negative” enhancers; DNA sequence which
binds repressors preventing RNA polymerase from
initiating transcription
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10.  Direct methylation of DNA
 Methyltransferases –
enzymes that add a methyl
group
 Common in CpG sequences
• “Cytosine – phosphate-Guanine”
 In mammals, 70 – 80% of
CpG sites are methylated
 Repression mechanism:
• Blocks transcription factors

11.  Enhancers:
• Specific sequence in DNA
• Short series of bases
• Vary in location
• Can be far away from gene regulated
• Bound by transcriptional activators (molecules from
inside or outside the cell that aid in transcription)
 Silencers
• Specific sequence of DNA
• Short series of bases
• Bind proteins that promote assembly of large protein
complexes that block transcription
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12. Many enhancers cause
DNA looping
• Transcriptional activator
binds to enhancer
• Activator also interacts with
part of transcription complex
to recruit complex to gene
by bending DNA
• Complex then interacts with
promoter and recruits
polymerase holenzyme
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13. Enhancers are hard to find because:
• Variable in sequence from one gene to the next
• Short series of bases
• Vary in location
• Can be far away from gene regulated
So -- how do you find them?
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14.  “Reporter Constructs”
• Put region of interest (with
regulatory elements) upstream
of an inducible gene (such as
lacZ)
• Modify (by deletion or
substitution) presumed
regulatory region
• Modifications that alter
expression of inducible gene
are regulatory elements
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15.  mRNA processing results
in same mature mRNA
 Alternative promoters
allow for different
regulation of same gene
• Larval vs. adult expression
 Fetal gamma-globin to adult
beta-globin in humans
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 Some genes have more than one promoter sequence
 Different promoters produce different primary
transcripts

16.  3 major domains:
• DNA binding domain
• Activating domain – interacts with initiation complex
proteins
• Protein-protein interaction domain
 Major transcription factor families
• Homeodomain – Hox genes (axis formation)
• Basic helix-loop-helix – muscle & nerve specification
• Basic leucine zipper – liver & fat cell differentiation
– Zinc Finger - segmentation, secondary sex determination,
metamorphosis, limb development
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