Control of Eukaryotic
Gene Expression
Eukaryotic Gene Regulation
Prokaryotic regulation is different from eukaryotic
regulation.
1. Eukaryotic cells have many more genes (23,700 in
human cells) in their genomes than prokaryotic
cells (average 3000).
2. Physically there are more obstacles as eukaryotic
chromatin is wrapped around histone proteins.
3. There are more non-histone proteins that are used
in eukaryotic gene expression than in prokaryotic
gene expression.
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Eukaryotic Gene Regulation in
Multicellular Organisms
• Almost all the cells in an organism are
genetically identical or totipotent.
• Differences between cell types result from
differential gene expression -- the
expression of different genes by cells with
the same genome.
• Errors in gene expression can lead to
diseases including cancer.
• Gene expression is regulated at many
stages.
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Organization
of DNA
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Types of Repetitive DNA
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Altering the Genome is a Form of Gene
Regulation
• Gene amplification- In amphibian
ovum there are over 1 million copies
of the rRNA made from tiny circles
of DNA in the nucleoli.
• Gene Loss-In gall midges (an insect) during
development, all but two cells lose 32 of their 40
chromosomes during the first mitotic divisions. These
cells that retain 40 chromosomes will produce gametes.
• Transposed genes-The hemoglobin gene has been
duplicated, mutated, and transposed to other
chromosomes to produce multiple but different copies
of the same gene.
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Gene Duplication and Transposition
Regulates Genes
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Rearrangement Gene
Domains Regulates Genes
• B lymphocytes can
produce millions of
different types of
antibodies
(proteins) that
react with millions
of different
antigens. This
happens by
rearrangement of
AB genes.
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Epigenetics
• Epigenetics refers to processes that
influence gene expression or function
without changing the underlying DNA
sequence.
1. Acetylation
2. Methylation
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Acetylation
• Acetylation of lysine found on the histone decreases the
affinity of histones for DNA and other histones, thereby
making DNA more accessible for transcription.
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Methylation
• A methyl group can be added to the nitrogenous bases of
cytosine that are followed by guanine. Many human genes
have upstream CG-rich regions called CpG islands.
Methylation of a gene's CpG island represses gene
expression. Different cells have different methylation
patterns, which contributes to the differences in gene
expression in different cell types.
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Role of Transcription Factors
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Role of Transcription Factors
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Role of Transcription
Factors and Activators
• This illustrates how
different cells have
different activators
which activate
different genes.
• The liver cells need
the protein albumin
and not the protein
crystallin and the
lens cells do not
need albumin but do
need crystallin.
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Role of Transcription Factors and
Lactose Persistence
• The LCT gene produces the enzyme lactase which
digests lactose. Lactose is a disaccharide found in dairy
products. In order to be transcribed, the LCT gene needs
a regulatory protein coded for by the MCM6 gene. Most
humans after weaning cease to produce the regulatory
protein but a mutation in the gene will allow its continued
production through adulthood. This mutation causes a
condition called lactose persistence.
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Coordination of Expression of
Related Proteins in a
Biochemical Pathway
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Post-Transcriptional Control
Alternative Splicing
Alternative splicing
• Once the immature mRNA is made, it could be
processed in different ways to give rise to different
mature mRNA and thus different proteins.
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Example of Alternative Splicing the
Same Gene in Humans
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Post-Transcriptional Control and RNAi
Alternative
• mRNA molecules do
not remain functional
indefinitely. This
length of time can
affect the number of
protein product
synthesize.
• Small pieces of RNA
can interfere (RNAi)
with mRNA by being
complementary to a
small part of the
mRNA and tagging it
for destruction.
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Post-Transcriptional Control
and microRNA (miRNA)
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Post-transcriptional
control- siRNA
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Other Factors that Can Affect the Expression
of Genes-Post Transcription
• Chemical signals that regulate the mRNA
leaving the nucleus. Nearly half of all mature
mRNA never reaches the cytoplasm. There
must be some sort of inhibitor that will allow
certain mRNA to leave and others toremain.
• Degrading of the mRNA that affects its lifespan.
The life-span can be associated with the length
of the poly-A-tail. As it shortens, it aids other
enzymes with the removal of the 5'cap and
nucleases break down the mRNA. mRNA can
last from minutes to weeks.
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Post-translational
control- Ubiquitin
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Other Factors that Can Affect the Expression
of Genes- Post Translation
Post-translational control
• Modification of protein
product. Often amino
acids must be removed
in order for the protein
to be functional.
• Proteins are often
modified with prosthetic
groups to make them
functional.
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