Gene Expression in Eukaryotes
Changes in gene expression allow eukaryotic cells to
respond to changes in the environment and cause
distinct cell types to develop.
Eukaryotic DNA is packaged with proteins into
structures that must be opened before transcription can
In eukaryotes, transcription is triggered by regulatory
proteins that bind to the promoter and to sequences
close to and far from the promoter.
Once transcription is complete, gene expression is
Alternative splicing, which allows a single gene to code
for several different products.
Molecules that regulate the life span of mRNAs.
Activation or inactivation of protein products.
Cancer can develop when mutations disable genes that
regulate cell-cycle control genes.
The regulation of gene expression is more complex in
eukaryotes than in prokaryotes.
Differential gene expression is responsible for
creating different cell types, arranging them into
tissues, and coordinating their activity to form the
multicellular society we call an individual.
Mechanisms of Gene Regulation—An Overview
Like prokaryotes, eukaryotes can control gene
expression at the levels of transcription, translation,
Three additional levels of control are unique to
eukaryotes: Chromatin remodeling.
Regulation of mRNA life span or stability.
In eukaryotes, DNA is wrapped around proteins to
create a protein-DNA complex called chromatin.
RNA polymerase cannot access the DNA when it is
supercoiled within the nucleus.
The DNA near the promoter must be released from
tight interactions with proteins before transcription can
begin; this process is called chromatin remodeling.
RNA Processing and Control of mRNA Stability
Transcription results in a ―Primary RNA transcript‖
that must undergo RNA processing to produce a mature
mRNA stability, or the life span of the mRNA, can also
be used to control gene expression.
What Is Chromatin’s Basic Structure?
Chromatin has a regular structure with several layers of
Chromatin contains nucleosomes—repeating,
Nucleosomes consist of negatively charged DNA
wrapped twice around eight positively charged histone
A histone protein called H1 functions to maintain the
structure of each nucleosome.
Between each pair of nucleosomes there is a ―linker‖
stretch of DNA.
H1 histones also may interact with each other and with
histones in other nucleosomes to form a tightly packed
structure called a 30-nanometer fiber. These 30-nanometer fibers in turn may form higher-
Chromatin’s elaborate structure not only allows the
DNA to be packaged in the nucleus, it also plays a key
role in regulating gene expression.
Chromatin Structure Is Altered in Active Genes
As in bacteria, eukaryotic DNA has sites called
promoters where RNA polymerase binds to initiate
Studies support the idea that chromatin must be
relaxed or decondensed for RNA polymerase to
bind to the promoter.
condensed DNA Is Protected from DNase
DNase is an enzyme that cuts DNA at random locations.
The enzyme cannot cut DNA when it is tightly
complexed with histones.
How Is Chromatin Altered?
Two major types of protein are involved in modifying
ATP-dependent chromatin-remodeling complexes
Other enzymes catalyze the acetylation (addition of
acetyl groups CH 3OO- and methylation (addition of
methyl groups CH -3 of histones.
Acetylation of histones is usually associated with
activation of genes. Methylation can be correlated with
either activation or inactivation
One type of acetylation enzyme is called histone
acetyl transferases (HATs). They add negatively
charged acetyl groups to the positively charged lysine
residues in histones. This acetylation reduces the positive charge on the
histones, decondensing the chromatin and allowing
Enzymes called histone deacetylases (HDACs) then
remove the acetyl groups from histones. This reverses
the effects of acetylation and allows chromatin
Chromatin Modifications Can Be Inherited
The pattern of chemical modifications on histones
varies from one cell type to another.
The histone code hypothesis contends that precise
patterns of chemical modifications of histones contain
information that influences whether or not a particular
gene is expressed.
Daughter cells inherit patterns of histone modification,
and thus patterns of gene expression, from the parent
This is an example of epigenetic inheritance,
patterns of inheritance that are not due to differences in
Imagine you’ve isolated a yeast mutant that contains
histones resistant to acetylation. What phenotype do you
predict for this mutant?
a. The mutant will grow rapidly
b. The mutant will show generally low levels of gene
c. The mutant will show generally high levels of gene
d. The mutant will show low levels of gene expression for
only a few select genes
Regulatory Sequences and Regulatory Proteins Eukaryotic promoters are similar to bacterial
promoters. There are three conserved sequences and
each eukaryotic promoter has two of the three.
The most common sequence is the TATA box.
All eukaryotic promoters are bound by the TATA-
binding protein (TBP).
Some Regulatory Sequences Are Near the Promoter
Regulatory sequences are sections of DNA that are
involved in controlling the activity of genes. When
regulatory proteins bind these sequences, they cause
gene activity to change.
Some eukaryotic regulatory sequences are similar to
those in bacteria, others are very different.
Yeast metabolize the sugar galactose. In the presence of
galactose, transcription of the five galactose-utilization
genes increases dramatically.
Mutant cells fail to produce any of the enzymes
required for galactose metabolism, leading to three
The five genes are regulated together even though they
are on different chromosomes.
Normal cells have a CAP-like regulatory protein that
exerts positive control over the five genes.
The mutant cells have a loss-of-function mutation that
completely disables the regulatory protein.
Promoter-proximal elements are located just
upstream of the promoter and the transcription start
site, and have sequences that are unique to specific
genes, providing a mechanism for eukaryotic cells to
exert precise control over transcription. Some Regulatory Sequences Are Far from the
While exploring how human immune system cells
regulate genes that produce antibodies, Susumu
Tonegawa and colleagues discovered that the intron,
rather than the exon, contains a regulatory sequence
required for transcription to occur.
The results were remarkable because:
The regulatory sequence was far from the promoter.
The regulatory sequence was downstream, rather than
upstream, from the promoter.
Regulatory elements that are far from the promoter are