Regulation of Eukaryotic Gene Expression

ILOS:
1. Enumerate levels of regulation of gene expression.
2. Discuss chromatin structure modifications & Epigenetic control.
3. Discuss Transcriptional initiation control by transcription factors &
hormone response elements.
4. Stability of mRNA transported into the cytoplasm.

Total No of genes: prokaryotes - 4000

eukaryotes – 35000
Gene expression: Multistep process that results in the production of
functional gene product (protein, enzyme, hormone etc.)
Importance of gene expression
o Cellular differentiation
o Morphogenesis
o Adaptability of organism
BIOCHMISTRY DEP 2018 2019
BIOCHMISTRY DEP 2018 2019
Types of Genes
1) Constitutive genes (Housekeeping genes):
Expressed at a logically constant rate
Not subjected to regulation
eg: enzymes of glycolysis
2) Regulated genes expressed only under certain conditions
expressed in all cells / subtypes of cells
eg: expression of insulin gene in pancreas
Inducible gene: Expression increases in response to inducer or
activator eg: bile acid induces ALP (alkaline phosphatase)
Repression: Inhibition of gene expression by repressor
eg: inhibition of ALA synthase by heme
Types of Gene Expression Regulation
1) Positive regulation: Increased gene expression: regulator /
enhancer / activator
2) Negative regulation: Reduced gene expression (Negative
regulation): regulator / silencer / repressor
Regulation of Gene Expression
1. Gene expression can be modulated by:
o Control of transcription
o Post transcriptional modifications
o Gene amplification
o Gene rearrangements
o Control of translation
o Protein modification / stabilization
2. Gene regulation is influenced by hormones, heavy metals
and chemicals
Regulation of Gene Expression at Prokaryotes
▪ Regulation occurs at transcription
▪ Operon; Genes involved in a metabolic pathway array
▪ Cistron; when present in a linear Smallest unit of gene expression
▪ Polycistronic mRNA: A single mRNA that encodes more than one
separately translated protein. eg - lac operon mRNA
Operon Concept of Gene Regulation
• Lactose metabolism in E.Coli (intestinal bacteria)
• Lac Operon
▪ Structural gene
▪ Inhibitor gene
▪ Promoter / Operator areas
▪ Repression – Derepression mechanism

Structural gene
1. lacZ : β- galactosidase (lactase)
2. lacY: galactoside permease
3. lacA: thiogalactoside transacetylase
Inhibitor gene: lacI: LacI (lac operon repressor protein)
Promoter site: Transcription of structural genes
Operator site: binding of lac repressor
Regulation Lac Operon
• Absence of lactose: reduced synthesis of lactose metabolizing
enzymes
• Presence of lactose : increased enzyme synthesis
• Presence of lactose and glucose : reduced synthesis of enzymes

• When both glucose and lactose are present, the genes for lactose
metabolism are transcribed to a small extent.
• Maximal transcription of the lac operon occurs only when glucose
is absent and lactose is present.
• The action of cyclic AMP and a catabolite activator protein
produce this effect.

BIOCHMISTRY DEP 2018 201

Difference between Euokarotic and Prokaryotic Genome
Eukaryote genome is complex
DNA is extensively folded and
packed into chromatin (protein – DNA complex).
Differences between eukaryotic and prokaryotic gene regulation:
• Genes (prokaryotes) are not organized into operon
• Separation of transcription and translation (eukaryotes)
• RNA processing (eukaryotes): capping at 5’ ends, addition of poly
A tail at 3’ end splicing
Regulation of Eukaryotic Gene Expression
1. Regulation at transcription level
❖ Chromatin remodeling
❖ Enhancers
❖ Trans acting molecules – DNA binding proteins; function as
transcriptional factors Cis-acting regulatory elements
eg: Hormone response elements
2. Regulation by post transcriptional process:
• Alternative mRNA splicing
• mRNA editing
3. Gene amplification
4. Gene rearrangement
Chromatine Remodelling

Enhancers
DNA elements which facilitate / enhance the initiation of
transcription at the promoter
Features
• Is active only when it exists within the same DNA molecule (cis to
the promoter)
• Work when located long distances from the promoter
• Work when upstream or downstream from the promoter
Enhancer work by :
o Binding one or more proteins
o Facilitating binding of the basal transcription complex to the
promoter
o Recruiting chromatin-modifying co regulatory complexes
o Insulators: prevents the enhancer function
Gene Amplification
1-Increases the number of genes available for transcription eg: resistance
to methotrexate by cancer cells cancer cells
2-increase the number of genes for dihydrofolate reductase (DHFR) drug
resistance
Gene Rearrangement
• Occurs during immunoglobulin synthesis
• IgG light chain mRNAs are coded by different
1. segments/domains
2. variable (VL) =300 coding sequences joining (JL) = 5
3. constant (CL) = 10
• Difficult for immune cells to achieve immunological specificity

Alternative RNA Processing

Primary transcript is processed differently in different tissues
Achieved by Alternative transcription start sites
Alternative polyadenylation site
Alternative splicing and processing
Regulation of mRNA Stability
1-Ends of mRNA: 5’ cap structure: prevents attack by 5’ exonuclease
& 3’ poly (A) tail: prevents attack by 3’ exonuclease
2-Ribonucleoprotein particles